Increased levels of 8-hydroxy-2'-deoxyguanosine attributable to carcinogenic metal exposure among schoolchildren.Arsenic, chromium, and nickel are reported in several epidemiologic studies to be associated with lung cancer lung cancer, cancer that originates in the tissues of the lungs. Lung cancer is the leading cause of cancer death in the United States in both men and women. Like other cancers, lung cancer occurs after repeated insults to the genetic material of the cell. . However, the health effects of arsenic, chromium, and nickel exposures are equivocal EQUIVOCAL. What has a double sense.
2. In the construction of contracts, it is a general rule that when an expression may be taken in two senses, that shall be preferred which gives it effect. Vide Ambiguity; Construction; Interpretation; and Dig. for children. Therefore, we performed a cross-sectional study cross-sectional study
See synchronic study.
n the scientific method for the analysis of data gathered from two or more samples at one point in time. to investigate possible associations between the internal concentrations of arsenic, chromium, and nickel and the level of oxidative stress oxidative stress,
n an imbalance of the prooxidant antioxidant ratio in which too few antioxidants are produced or ingested or too many oxidizing agents are produced. to DNA DNA: see nucleic acid.
or deoxyribonucleic acid
One of two types of nucleic acid (the other is RNA); a complex organic compound found in all living cells and many viruses. It is the chemical substance of genes. in children. We measured urinary levels of arsenic, chromium, and nickel for 142 nonsmoking non·smok·ing
1. Not engaging in the smoking of tobacco: nonsmoking passengers.
2. Designated or reserved for nonsmokers: the nonsmoking section of a restaurant. children using atomic absorption spectrometry Absorption spectrometry
A scientific procedure to determine chemical makeup of samples.
Mentioned in: Herbalism, Traditional Chinese . As a biomarker for oxidative stress, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were analyzed with an enzyme-linked immunosorbent assay enzyme-linked immunosorbent assay
Enzyme-linked immunosorbent assay (ELISA)
A diagnostic blood test used to screen patients for AIDS or other viruses. kit. The median urinary 8-OHdG level for our subjects was 11.7 ng/mg creatinine creatinine /cre·at·i·nine/ (kre-at´i-nin) an anhydride of creatine, the end product of phosphocreatine metabolism; measurements of its rate of urinary excretion are used as diagnostic indicators of kidney function and muscle mass. . No obvious relationship between the levels of urinary nickel and 8-OHdG was found. Multiple linear regression Linear regression
A statistical technique for fitting a straight line to a set of data points. analysis showed that children with higher urinary chromium had greater urinary 8-OHdG than did those with lower urinary chromium. Similarly, subjects with higher urinary arsenic had greater urinary 8-OHdG than did those with lower urinary arsenic. Furthermore, children with both high urinary arsenic and high urinary chromium had the highest 8-OHdG levels (mean [+ or -] SE, 16.0 [+ or -] 1.3; vs. low arsenic/low chromium, p < 0.01) in urine, followed by those with low arsenic/high chromium (13.7 [+ or -] 1.6; vs. low arsenic/low chromium, p = 0.25), high arsenic/low chromium (12.9 [+ or -] 1.6 vs. low arsenic/low chromium, p = 0.52), and low arsenic/low chromium (11.5 [+ or -] 1.3); the trend was significant (p < 0.001). Thus, environmental carcinogenic carcinogenic
having a capacity for carcinogenesis. metal exposure to chromium and arsenic may play an important role in oxidative DNA damage to children. Key words: arsenic, children, chromium, 8-hydroxy-2'-deoxyguanosine, nickel.
Potential hazardous pollutants from industrial sources such as thermal power plants are often emitted to our living environments, where they possibly expose adults and children to heavy metals heavy metals,
n.pl metallic compounds, such as aluminum, arsenic, cadmium, lead, mercury, and nickel. Exposure to these metals has been linked to immune, kidney, and neurotic disorders. through inhalation and ingestion ingestion /in·ges·tion/ (-chun) the taking of food, drugs, etc., into the body by mouth.
1. The act of taking food and drink into the body by the mouth.
2. of contaminated contaminated,
v 1. made radioactive by the addition of small quantities of radioactive material.
2. made contaminated by adding infective or radiographic materials.
3. an infective surface or object. soil and dust. Earlier literature pointed out that increased use of cod for power production will lead to increased release of metals into the environment (Sabbioni et al. 1984). Furthermore, high quantities of arsenic, chromium, and nickel are detected in milled coal and ash of coal-fired power plants (Goodarzi and Huggins 2001), and these three metals are also reportedly associated with human lung The human lungs are the human organs of respiration.
Humans have two lungs, with the left being divided into two lobes and the right into three lobes. Together, the lungs contain approximately 1500 miles (2,400 km) of airways and 300 to 500 million alveoli, having a total cancers in several occupational epidemiologic studies (Chen and Chen 2002; Droste et al. 1999; Grimsrud et al. 2002). However, the health effects of arsenic, chromium, and nickel exposure are especially equivocal for children. Children are considered to be a population susceptible to adverse health effects induced by air pollutants (Nicolai 1999). Previous studies of metal exposure to children in Taiwan focused primarily on lead in occupational sites (Wang et al. 2002) and Chinese herbal medicine Chinese herbal medicine
see herbal medicine. (Cheng et al. 1998), whereas effects of other environmental contaminants such as arsenic, chromium, and nickel on children's health Children's Health Definition
Children's health encompasses the physical, mental, emotional, and social well-being of children from infancy through adolescence. have been largely ignored.
The carcinogenic potential of arsenic, chromium, and nickel compounds is well established for humans and experimental animals (Hayes 1997). However, the molecular damage formation after exposure to metals is still not well understood. One mechanism proposed frequently is an increase in oxidative DNA lesions attributable to metal exposure, mediated by increased generation of highly reactive oxygen species reactive oxygen species,
n molecules and ions of oxygen that have an unpaired electron, thus rendering them extremely reactive. Many cellular structures are susceptible to attack by ROS contributing to cancer, heart disease, and cerebrovascular disease. (ROS ROS,
n.pr See reactive oxygen species. ) (Dally and Hartwig 1997; Kasprzak 1991; Kasprzak et al. 1997). Oxidative DNA lesions are supposed to play important roles in various diseases including cancer and premature aging (Beckman and Ames 1998; Cerutti 1994; Grisham 1994; Jenner 1994; Witztum 1994). Among the diverse oxidative DNA lesions, 8-hydroxy-2'-deoxyguanosine (8-OHdG) is one of the most abundant base modifications and has attracted special attention because it is premutagenic, causing G-to-T transvcrsions (Cheng et al. 1992); thus, the presence of 8-OHdG may lead to mutagenesis mutagenesis /mu·ta·gen·e·sis/ (mu?tah-jen´e-sis)
1. the production of change.
2. the induction of genetic mutation.
n. pl. . Moreover, the repair process for 8-OHdG-inflicted damage results in excised 8-OHdG adduct adduct /ad·duct/ (ah-dukt´) to draw toward the median plane or (in the digits) toward the axial line of a limb.
adduct /ad·duct/ (a´dukt) inclusion complex. being excreted into the urine (Marnett 2000; Shigenaga et al. 1989). Because of easy collection, urinary 8-OHdG is thus regarded as a suitable biomarker of oxidative stress (Toraason 1999; Wong et al. 2003).
To investigate possible associations between the incorporated internal concentrations of arsenic, chromium, and nickel and the level of oxidative stress in schoolchildren schoolchildren school npl → écoliers mpl;
(at secondary school) → collégiens mpl; lycéens mpl
schoolchildren school , we performed a cross-sectional study in Taiwan.
Materials and Methods
Study areas and subject selection. The study subjects were nonsmoking fifth-grade pupils (10-12 years of age) who in January 2003 were attending three elementary schools from three different towns of Taichung County , Taiwan. Each selected primary school was close to, and within 1 km of, an ambient air quality monitoring station. Of these schools, Longgang elementary school is also adjacent to the Taichung Thermal Power Plant on the southern side of Taichung harbor, with eight coal-fired generation units in operation to accommodate a total installed capacity of 4,688 MW. The coal consumption of this power plant is approximately 1.28 million tons per year. Coal is stored at and delivered from three coal yards (storage capacity, 310, 0.52, and 0.42 million tons, respectively) near the power plant. Thus, it is possible that coal particles are emitted into the atmosphere from these three coal yards. Additionally, there were no major roads or factories within the Longgang elementary school district. The remaining schools, Shalach and Shuntian, are located in suburban communities and are on the northeastern upwind side approximately 8 and 18 km of the Taichung Thermal Power Plant, respectively. In addition, these two school districts are intersected by major trunk roads. Taichung County (Traditional Chinese: 臺中縣 or 台中縣; Hanyu Pinyin: Táizhōng Xiàn; Tongyong Pinyin: Táijhong Siàn;
All subjects who participated in the medical surveillance process underwent physical examinations conducted by a qualified pediatrician. All participating schoolchildren voluntarily entered the study after informed written consent was obtained from the children's parents. Parents of schoolchildren completed the questionnaire before collecting children's urine samples. The questionnaire was divided into the following parts: demographic data of the children, respiratory symptoms and diseases of the children, smoking habits and occupation of the parents, and possible sources of indoor air pollution such as household smoking, pet feeding, incense burning all day, and home dampness. According to according to
1. As stated or indicated by; on the authority of: according to historians.
2. In keeping with: according to instructions.
3. the responses to the questionnaires, asthma was assessed by the question "has your child had wheezing Wheezing Definition
Wheezing is a high-pitched whistling sound associated with labored breathing.
Wheezing occurs when a child or adult tries to breathe deeply through air passages that are narrowed or filled with mucus as a in the chest accompanied by dyspnea dyspnea /dysp·nea/ (disp-ne´ah) labored or difficult breathing.dyspne´ic
paroxysmal nocturnal dyspnea that had ever been given the diagnosis of asthma by a physician during the past 12 months?" Similarly, children who had been diagnosed as having allergic rhinitis Allergic Rhinitis Definition
Allergic rhinitis, more commonly referred to as hay fever, is an inflammation of the nasal passages caused by allergic reaction to airborne substances. by a physician were considered to have a history of allergic rhinitis. Of these study subjects, 16 schoolchildren were excluded from the study because of incomplete urine samples or residence far from the school. Finally, a total of 142 subjects without any disease history except respiratory diseases participated in this study.
Urine collection. In our study period, spot morning urine samples were collected in polypropylene specimen containers. The decision to use first morning voids rather than 24-hr collections was based on the report by Thompson et al. (1999), which indicated that 24-hr average urinary levels were not statistically different in values from first voids. Moreover, it is difficult to collect 24-hr urine samples and first voids of morning urine from every subject. Finally, most morning urine specimens we obtained were first spot and small numbers of them were second spot specimens. Immediately after the collection, urine samples were stored at -20[degrees]C until used for analysis.
Measurement of metal levels in urine. Metal levels in urine samples including arsenic, chromium, and nickel were measured using atomic absorption spectrometry with a graphite furnace (model 4110ZL; Perkin-Elmer, Norwalk, CT, USA) technique and Zeeman background correction. All analytical glassware and plasticware purchased were of low-metal grade and were further cleaned with diluted nitric acid nitric acid, chemical compound, HNO3, colorless, highly corrosive, poisonous liquid that gives off choking red or yellow fumes in moist air. It is miscible with water in all proportions. before use. Initially, all the frozen samples were thawed and aliquotted at room temperature. A solution of Triton X-100 (0.1%, wt/vol) was prepared in nitric acid (0.2%, vol/vol). Subsequently, the 18-mL urine samples were diluted with 2 mL of prepared Triton X-100 solution (9:1) and stored at -20[degrees]C until required for analysis. Urine test portion and aqueous standards were injected at 20 [micro]L using the autosamplers in the furnace. We used a mixture containing palladium plus magnesium nitrate Magnesium nitrate is a hygroscopic salt with the formula Mg(NO3)2. In air, it quickly forms the hexahydrate with the formula Mg(NO3)2.6H2O. It is very soluble in both water and ethanol. , and magnesium nitrate as chemical modifiers for the determination of arsenic and chromium in urine, respectively. No matrix modifier (programming) modifier - An operation that alters the state of an object. Modifiers often have names that begin with "set" and corresponding selector functions whose names begin with "get". was used for the determination of nickel. For analyses of urinary metals, we checked the accuracy of the instrumental methods and the analytical procedure by using reference solutions (standard reference material 12111, normal-range metals urine toxicology control; UTAK Laboratories, Valencia, CA, USA), which were run before every batch of samples. The correlation coefficients for each of the values of the standard curves were all > 0.990. The mean recovery rates ranged from 90 to 105%, and coefficients of variation for reproducibility were all < 10%. Metal concentrations in urine were corrected for each individual according to their urinary creatinine values, and urinary samples were analyzed blind to the status of the individuals for the presence of metals.
Determination of urinary 8-OHdG levels. Before examination, urine samples were centrifuged at 2,000 x g for 10 min to remove any suspended cell debris. The supernatants were used for the determination of 8-OHdG levels using a competitive enzyme-linked immunosorbent assay kit (ELISA ELISA (e-li´sah) Enzyme-Linked Immuno-Sorbent Assay; any enzyme immunoassay using an enzyme-labeled immunoreactant and an immunosorbent.
n. ; Japan Institute for the Control of Aging, Fukuroi, Japan). The determination range was 0.5-200 ng/mL. The 8-OHdG monoclonal antibody monoclonal antibody, an antibody that is mass produced in the laboratory from a single clone and that recognizes only one antigen. Monoclonal antibodies are typically made by fusing a normally short-lived, antibody-producing B cell (see immunity) to a fast-growing N45.1 and urine sample were loaded at 50 [micro]L onto a microtiter plate A Microtiter plate or microplate is a flat plate with multiple "wells" used as small test tubes. The microplate has become a standard tool in analytical research and clinical diagnostic testing laboratories. that was coated with 8-OHdG, and incubated at 37[degrees]C for 60 min, in accordance with the instructions of the manufacturer. After the wells were washed three times, the antibodies that remained bound to the 8-OHdG in the sample were further bound with the horseradish horseradish
Hardy perennial plant (Armoracia lapathifolia) of the mustard family, native to Mediterranean lands and grown throughout the temperate zones. Its hotly pungent, fleshy root is used as a condiment and is traditionally considered medicinal. peroxidase-conjugated secondary antibody A secondary antibody is an antibody that binds to primary antibodies or antibody fragments. They are typically labeled with probes that make them useful for detection, purification or cell sorting applications. , followed by incubation at 37[degrees]C for 60 min. The wells were again washed three times. Subsequently, a substrate containing 3,3',5,5'-tetramethylbenzidine was added, and the wells were incubated at room temperature for 15 rain, resulting in the development of color not of the white race; - commonly meaning, esp. in the United States, of negro blood, pure or mixed.
See also: Color intensity proportional to the amount of antibody bound to the plate. The color reaction A Color reaction (UK, Colour reaction) in analytical chemistry is a chemical reaction that is used to transform colorless chemical compounds into colored derivatives which can be detected visually with the aid of a color reagent. was terminated by the addition of stop solution (1 M phosphoric acid phosphoric acid, any one of three chemical compounds made up of phosphorus, oxygen, and hydrogen (see acids and bases). The most common, orthophosphoric acid, H3PO4, is usually simply called phosphoric acid. ), and the absorbance absorbance /ab·sor·bance/ (-sor´bans)
1. in analytical chemistry, a measure of the light that a solution does not transmit compared to a pure solution. Symbol .
2. was measured using a computer-controlled spectrophotometric plate reader at a wavelength of 450 nm. The concentration of 8-OHdG in the test samples was interpolated interpolated /in·ter·po·lat·ed/ (in-ter´po-la?ted) inserted between other elements or parts. from a standard curve drawn with the assistance of logarithmic logarithmic
pertaining to logarithm.
when the logs of two variables plotted against each other create a straight line. transformation. Urinary 8-OHdG levels were subsequently adjusted by urinary creatinine levels.
Statistical analysis. Because of the positively skewed distribution Skewed distribution
Probability distribution in which an unequal number of observations lie below (negative skew) or above (positive skew) the mean. of the urinary arsenic, chromium, and nickel levels, we used nonparametric testing to test the differences of urinary metal levels among our study children at three different elementary schools. Similarly, because of the positively skewed distribution of the urinary 8-OHdG levels, we used nonparametric testing to test the differences of urinary 8-OHdG level for each variable. Median values of urinary arsenic, chromium, and nickel levels were used as cutoff. Subsequently, we developed a multiple linear regression analysis to adjust for significant covariate identified in the univariate analysis to evaluate potential differences in urinary 8-OHdG. We also computed regression coefficients and their SEs and calculated least-square means to predict the adjusted 8-OHdG levels for children with different urinary metal contents.
In total, 142 children (74 boys and 68 girls) were involved in this study. Their ages ranged from 10 to 12 years (mean age, 11.2 years). All study subjects lived within the limits of the Taichung harbor area The Harbor Area is the area along the Port of Los Angeles. It contains neighborhoods of Los Angeles (including Wilmington & San Pedro). Los Angeles City neighborhoods in the Harbor Area
The median urinary metal levels were 6.4 [micro]g/L for arsenic, 1.9 [micro]g/L for chromium, and 3.4 [micro]g/L for nickel (Table 1). The creatinine-adjusted median levels were 7.7 [micro]g/g for arsenic, 2.0 [micro]g/g for chromium, and 4.1 [micro]g/g for nickel. Among the 142 urine samples, 19 urine samples were below the detection limit of 0.1 [micro]g/L urine for arsenic, 19 samples were below the detection limit of 0.7 [micro]g/L for chromium, and 16 samples were below the detection limit of 0.8 [micro]g/L for nickel. Especially, the study children at Longgang elementary school had significantly higher urinary levels of arsenic, chromium, and nickel than did those at Shalach and Shuntian elementary schools (p-values [less than or equal to] 0.01, Kruskal-Wallis test).
Median urinary 8-OHdG level for the study subjects was 11.7 ng/mg creatinine (range, 0.4-59.7 ng/mg creatinine) (Table 2). Children at Longgang elementary school had higher 8-OHdG levels than did those at Shalach and Shuntian elementary schools (p < 0.01, Kruskal-Wallis test). Children of mothers who had greater than a senior high school education had significantly lower 8-OHdG levels than did children of mothers who had less than a senior high school education (p = 0.04, Wilcoxon rank sum test). Children whose parents smoked at home also had significantly higher 8-OHdG levels than did children whose parents did not smoke at home (p = 0.07). Children with allergic rhinitis had significantly lower 8-OHdG levels than did those without allergic rhinitis (p = 0.02). However, sex (p = 0.94), paternal education (P = 0.70), parental occupation (0 = 0.11), pet feeding (p = 0.92), incense burning at home all day (o = 0.18), home dampness (0 = 0.40), and asthma history (p = 0.51) were not associated with increased urinary 8-OHdG levels.
Children with urinary arsenic levels > 7.7 [micro]g/g creatinine (median, n = 71) had higher 8-OHdG levels than did those with urinary arsenic levels < 7.7 [micro]g/g creatinine (n = 71, p = 0.09). Children with urinary chromium > 2.2 [micro]g/g creatinine (median, n = 71) "also had higher 8-OHdG levels than did those with urinary chromium levels < 2.2 [micro]g/g creatinine (n = 71, p = 0.06). However, children with urinary nickel levels > 4.1 [micro]g/g creatinine (median, n = 71) did not have higher 8-OHdG levels than those with urinary nickel levels < 4.1 [micro]g/g creatinine (n = 71, p = 0.62).
Our univariate analysis showed that only elementary school, maternal education, parental smoking status, history of allergic rhinitis, and urinary creatinine-adjusted concentrations of arsenic and chromium were obviously associated with elevated levels of urinary 8-OHdG (p-values < 0.10). Therefore, we performed a multiple linear regression model for urinary 8-OHdG level as a function of maternal education, parental smoking status, history of allergic rhinitis, and urinary creatinine-adjusted concentrations of arsenic and chromium [general linear model (GLM GLM Global Language Monitor
GLM Global Marine (stock symbol)
GLM Graduated Length Method (ski instruction)
GLM Good Looking Mom (used in pediatric practices)
GLM God Loves Me ); Table 3]. We excluded elementary school in this model because the variables of elementary school and urinary arsenic and chromium levels had high colinearity. Urinary 8-OHdG level was positively associated with maternal educational level below senior high school (p = 0.05) and was negatively associated with history of allergic rhinitis (0 = 0.05). However, parental smoking status (p = 0.47) appeared not to influence the concentrations of urinary 8-OHdG for individuals when examining the data using GLM analysis. Interestingly, a mean difference of 1.9 ng/mg creatinine for urinary 8-OHdG was noted for children with high urinary arsenic levels compared with those with low urinary arsenic levels (p = 0.18). Children with high urinary chromium levels also had a mean difference of 3.0 ng/mg creatinine for urinary 8-OHdG compared with those with low urinary chromium levels (0 = 0.04). Furthermore, in this model, the partial [R.sup.2] value was 17.5% for urinary arsenic and 21.5% for urinary chromium.
Subsequently, we performed a least-squares mean analysis to assess the urinary 8-OHdG levels of children with combination of urinary arsenic and chromium adjusted for maternal education and history of allergic rhinitis. Children with both low urinary arsenic and low urinary chromium levels had the lowest urinary 8-OHdG mean levels of 11.4 rig/rag creatinine (n = 44; Figure 1), whereas those with both high urinary arsenic and high urinary chromium levels had the highest urinary 8-OHdG mean levels of 16.2 ng/mg creatinine (n = 43; vs. low arsenic/low chromium, t0 < 0.01). Those with both low urinary arsenic and high urinary chromium levels (13.7 ng/mg creatinine, n = 28; vs. low arsenic/low chromium, p = 0.25) and those with both high urinary arsenic and low urinary chromium levels (12.7 ng/mg creatinine, n = 27; vs. low arsenic/ low chromium, p = 0.52) had a moderately increased 8-OHdG mean levels. This trend in urinary 8-OHdG levels was statistically significant (p = 0.01, GLM). Furthermore, the difference in urinary 8-OHdG levels between the combination high urinary arsenic and chromium and combination low urinary arsenic and chromium (4.8 ng/mg creatinine) was greater than the summation summation n. the final argument of an attorney at the close of a trial in which he/she attempts to convince the judge and/or jury of the virtues of the client's case. (See: closing argument) of differences of urinary 8-OHdG levels between the combination low urinary arsenic and high urinary chromium and combination low urinary arsenic and low urinary chromium (2.3 ng/mg creatinine), and combined high urinary arsenic and low urinary chromium with combined low urinary arsenic and low urinary chromium (1.3 ng/mg creatinine).
Attacks on DNA by ROS frequently result in oxidative DNA damage. 8-OHdG is a modified base that occurs in DNA because of attack by hydroxyl radicals. Because it is premutagenic, causing G-to-T transversions (Cheng et al. 1992), the presence of 8-OHdG may lead to mutagenesis. The possibility of 8-OHdG arising from oxidation of deoxyguanosine has been also proposed (Shigenaga et al. 1989), and the result of this deoxyguanosine oxidation does not occur in DNA, so this 8-OHdG has no mutagenic mutagenic
inducing genetic mutation. potential. Thus, urinary 8-OHdG is commonly considered a biomarker of oxidative stress, reflecting its repair from DNA. Nonetheless, urinary 8-OHdG has not been used in previous studies to detect the effects of environmental carcinogenic metal exposure in children. In our study, the median value (11.7 ng/mg creatinine) of urinary 8-OHdG for our participants was similar to that of a previous study for normal English children (10.0 ng/mg creatinine) (Drury et al. 1998).
A major fraction of arsenic, chromium, and nickel absorbed by humans appears to be eliminated relatively quickly and mainly via urine. The biologic half-life for these metals has been estimated to be between 1 and 3 days (Hwang et al. 1997; Paustenbach et al. 1997; Sunderman 1993; Vahter 1994). Thus, these metal concentrations in urine samples are determined as important short-term exposure biomarkers and have been used in many epidemiologic studies (Moore et al. 1997; Smith-Sivertsen et al. 1998; Stern et al. I998). In the present study, we found statistically significant relationships between the urinary concentrations of chromium and arsenic and the level of DNA oxidative stress. The lack of correlation between exposure to nickel and DNA oxidative stress could be attributable to a low biologically relevant dose in the study population. Several studies have demonstrated that arsenic and chromium cause oxidative DNA damage to cultured cells (Kessel et al. 2002; Yuann et al. 1999). Previous epidemiologic studies have also shown increased 8-OHdG levels in humans exposed to arsenic (Matsui et al. 1999) or chromium (Kuo et al. 2003). Transition metals are commonly thought to produce ROS such as hydroxyl radicals that can directly damage cellular DNA. The other mechanism is indirect oxidative DNA damage due to inflammation caused by metal exposure (Donaldson et al. 2002). Some metals may stimulate the defense systems of the body so that they react against the toxic damage to produce cytokines Cytokines
Chemicals made by the cells that act on other cells to stimulate or inhibit their function. Cytokines that stimulate growth are called "growth factors. (Carter et al. 1997; Donaldson et al. 2002). Several cytokines cause production of large amounts of ROS. Some propose that ROS generated in inflamed tissues can cause injury to target cells and also damage DNA, which contributes to carcinogenic processes (Chazotte-Aubert et al. 1999; Eiserich et al. 1998).
Environmentally relevant metals seldom occur alone. Little is known about the exact mechanism of carcinogenesis car·ci·no·gen·e·sis
The production of cancer.
production of cancer.
viruses and some parasites are capable of initiating neoplasia. of two or more metals when they are present together. It is generally assumed that the concept of additivity is operative on low-level exposures to chemical mixtures (Hartwig and Schwerdtle 2002). It is particularly interesting that we observed a synergistic effect Synergistic effect
A violation of value-additivity in that the value of a combination is greater than the sum of the individual values. for combined arsenic and chromium exposure on DNA oxidative stress in the present study (Figure 1). It may be that other types of cellular damage are caused by metal exposure, which also contributes to their carcinogenic potentials. There is accumulating evidence that metals including arsenic and chromium can interfere with distinct steps of diverse DNA repair DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as UV light can cause DNA damage, resulting in as many as 1 systems (Hartwig and Schwerdtle 2002). Thus, oxidative DNA lesions are not only induced by metals at biologically relevant concentrations, but their extent may also be enhanced indirectly by impaired repair. Further studies are required to clarify these findings.
The amount of the modified base in cellular DNA excreted into urine should represent the average rate of DNA damage in the whole body (Cooke et al. 2000). Thus, it is possible that the levels of oxidative DNA damage are reflective of different active diseases, especially active inflammation (Wong et al. 2003). Besides, urinary levels of any oxidative lesion rely on efficient renal excretion of the damage products, so renal impairment can therefore affect urinary 8-OHdG levels (Akagi et al. 2003). In our study, urinary creatinine levels were used to correct for variation in urine concentration. In addition, no medical histories were reported by our participants except asthma and allergic rhinitis. There is ample evidence indicating that allergic disorders, such as asthma and rhinitis Rhinitis Definition
Rhinitis is inflammation of the mucous lining of the nose.
Rhinitis is a nonspecific term that covers infections, allergies, and other disorders whose common feature is the location of their symptoms. , are mediated by oxidative stress (Bowler and Crapo 2002). In our study, we did not observe a significant association between asthma and urinary 8-OHdG level in children. On the contrary, children with allergic rhinitis had significantly lower 8-OHdG than did those without. One could interpret this finding as an effect rather than a cause; that is, children with past allergies or past episodes of respiratory symptoms have had previous medical care, and their parents may have been urged to improve their environment to alleviate the symptoms. We also found that maternal education level, used as a proxy for socioeconomic status socioeconomic status,
n the position of an individual on a socio-economic scale that measures such factors as education, income, type of occupation, place of residence, and in some populations, ethnicity and religion. , was significantly related to children's oxidative DNA damage. Maternal education may convey information that influences the patterns of potential metal exposure as well as health care for children. In addition, we also observed that children whose parents smoked had higher 8-OHdG expression, although it was not significant in our multiple linear regression model. Because cigarette smoke contains ROS, the association between cigarette smoking and urinary 8-OHdG has been previously reported (Loft and Poulsen 1996). However, the association between 8-OHdG and children exposed to environmental tobacco smoke environmental tobacco smoke (ETS/passive smoke),
n the gaseous by-product of burning tobacco products, including but not limited to commercially manufactured cigarettes and cigars; contains toxic elements harmful to the health of adults and children has not been investigated. Oxidative damage occurs rapidly after exposure, and this damage can be repaired rapidly. Because Taiwanese children may not have regular chances to be exposed to tobacco smoke from their family members, the effects of passive smoking on 8-OHdG in children are less likely to appear in the model.
Children spend their most of their time indoors. It is therefore important to consider the effects that exposure to indoor air pollutants may have on children's oxidative DNA damage. House dust and fungi are the major indoor pollutants in our subtropical sub·trop·i·cal
Of, relating to, or being the geographic areas adjacent to the Tropics.
of the region lying between the tropics and temperate lands
area (Li et al. 1994; Wang et al. 1999). In addition, burning Chinese incense releases polycyclic aromatic hydrocarbons polycyclic aromatic hydrocarbon
Any of a class of carcinogenic organic molecules that consist of three or more rings containing carbon and hydrogen and that are commonly produced by fossil fuel combustion. (Lung et al. 2003), which may increase cellular oxidative stress (Wu et al. 2003). Our data provide no evidence for an association between the levels of indoor environmental factors such as pet feeding, incense burning, and home dampness. In our study, these indicators were self-reported and therefore were subjective and could have resulted in misclassification of exposure that might reduce the observed associations.
When the balance between pro-oxidant and antioxidant antioxidant, substance that prevents or slows the breakdown of another substance by oxygen. Synthetic and natural antioxidants are used to slow the deterioration of gasoline and rubber, and such antioxidants as vitamin C (ascorbic acid), butylated hydroxytoluene processes is shifted in favor of the former, increased 8-OHdG would be generated from further DNA oxidation The introduction to this article provides insufficient context for those unfamiliar with the subject matter.
Please help [ improve the introduction] to meet Wikipedia's layout standards. You can discuss the issue on the talk page. and ring opening followed by rearrangements (Cadet et al. 2003). However, the role of pro-oxidant and antioxidant on 8-OHdG in our study children was not identified. In addition, the 8-OHdG monoclonal antibody used in our ELISA assay has similar binding affinity for the oxidized oxidized
having been modified by the process of oxidation.
see absorbable cellulose. free base 8-hydroxyguanine, and the oxidized nucleoside nucleoside
Any of a class of organic compounds, including structural subunits of nucleic acids. Each consists of a molecule of a five-carbon sugar (ribose in RNA, deoxyribose in DNA) and a nitrogen-containing base, either a purine or a pyrimidine. 8-hydroxyguanosine (Fin et al. 1995). Thus, the possibility of overestimation of urinary 8-OHdG levels by our ELISA assay cannot be ruled out, and this bias would be likely to attenuate To reduce the force or severity; to lessen a relationship or connection between two objects.
In Criminal Procedure, the relationship between an illegal search and a confession may be sufficiently attenuated as to remove the confession from the protection afforded by the the observed association if it was nondifferential.
In our study, children's exposure to arsenic and chromium was associated with increased generation of subsequent 8-OHdG. However, the role of other carcinogenic metals on oxidative DNA damage also requires further study. For the future, a longitudinal rather than a cross-sectional study should be conducted to ascertain the possible association between carcinogenic metal exposure and oxidative DNA lesions. A longitudinal study longitudinal study
a chronological study in epidemiology which attempts to establish a relationship between an antecedent cause and a subsequent effect. See also cohort study. that includes a relevant number of environmentally exposed participants offers an advantage for studying dose-effect relationships over time with repeated measurements.
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Ruey-Hong Wong, Chung-Yih Kuo, Ming-Lin Hsu, Tsun-Yen Wang, Pi-I Chang, Tsung-Hsun Wu, and Shuai Huang
Department of Public Health, College of Health Care and Management, Chung Shan Medical University, Taichung, Taiwan
Address correspondence to R.-H. Wong, Department of Public Health, College of Health Care and Management, Chung Shah Medical University, 110 Chien-Kuo North Rd., Section 1, Taichung, Taiwan 40242. Telphone: 886-4-24730022, ext. 11792. Fax: 886-4-23248179. E-mail: rueyhong@ csmu.edu.tw
This study was supported by the Bureau of Environmental Protection of Taichung County, Taiwan, Republic of China.
The authors declare they have no competing financial interests.
Received 9 July 2004; accepted 26 May 2005.
Table 1. Concentrations of arsenic, chromium, and nickel in the study population. Elementary school Longgang Shalach Variable (n = 49) (n = 45) Arsenic ([micro]g/L urine) 16.2 [+ or -] 2.6 ** 8.7 [+ or -] 0.9 Arsenic ([micro]g/g urinary creatinine) 21.3 [+ or -] 4.3 ** 10.0 [+ or -] 1.2 Chromium ([micro]g/L urine) 2.6 [+ or -] 0.2 ** 1.9 [+ or -] 0.1 Chromium ([micro]g/g urinary creatinine) 3.7 [+ or -] 0.5 ** 2.2 [+ or -] 0.2 Nickel ([micro]g/L urine) 5.4 [+ or -] 0.5 * 3.9 [+ or -] 0.3 Nickel ([micro]g/g urinary creatinine) 7.2 [+ or -] 1.1 ** 4.6 [+ or -] 0.5 Elementary school All (n = 142) Shuntian Variable (n = 48) Mean [+ or -] SE Arsenic ([micro]g/L urine) 3.7 [+ or -] 0.6 9.1 [+ or -] 1.1 Arsenic ([micro]g/g urinary creatinine) 4.7 [+ or -] 0.7 12.1 [+ or -] 1.6 Chromium ([micro]g/L urine) 1.3 [+ or -] 0.1 1.9 [+ or -] 0.1 Chromium ([micro]g/g urinary creatinine) 2.0 [+ or -] 0.2 2.7 [+ or -] 0.2 Nickel ([micro]g/L urine) 2.8 [+ or -] 0.2 4.0 [+ or -] 0.2 Nickel ([micro]g/g urinary creatinine) 4.1 [+ or -] 0.5 5.4 [+ or -] 0.4 All (n = 142) Geometric Variable mean Median Maximum Arsenic ([micro]g/L urine) 3.9 6.4 86.4 Arsenic ([micro]g/g urinary creatinine) 5.0 7.7 149.3 Chromium ([micro]g/L urine) 1.7 1.9 6.6 Chromium ([micro]g/g urinary creatinine) 2.2 2.0 21.4 Nickel ([micro]g/L urine) 3.2 3.4 14.5 Nickel ([micro]g/g urinary creatinine) 4.0 4.1 47.8 All values shown are mean [+ or -] SE. * p = 0.01, ** p < 0.01, Kruskal-Wallis test. Table 2. Urinary 8-OHdG (ng/mg) creatinine stratified by different variables. Variable No. Mean [+ or -] SE Total 142 13.6 [+ or -] 0.7 Elementary school Longgang 49 18.8 [+ or -] 1.5 Shalach 45 9.8 [+ or -] 0.7 Shuntian 48 11.8 [+ or -] 0.9 Sex Boys 74 13.2 [+ or -] 0.9 Girls 68 14.0 [+ or -] 1.1 Paternal education (years) > senior high school ([greater than or equal to] 12) 83 12.8 [+ or -] 0.7 < senior high school (< 12) 59 14.7 [+ or -] 1.4 Maternal education (years) > senior high school ([greater than or equal to] 12) 73 11.8 [+ or -] 0.7 < senior high school (< 12) 69 15.5 [+ or -] 1.2 Parental occupation Industry 72 14.8 [+ or -] 1.1 Nonindustry 70 12.4 [+ or -] 0.9 Parental smoking status Yes 70 14.3 [+ or -] 0.9 No 72 12.9 [+ or -] 1.1 Possible indoor pollutants Pet feeding Yes 27 13.3 [+ or -] 1.6 No 115 13.7 [+ or -] 0.8 Incense burning at home all day Yes 58 14.5 [+ or -] 1.1 No 84 12.9 [+ or -] 0.9 Home dampness Yes 29 15.3 [+ or -] 2.1 No 113 13.1 [+ or -] 0.7 Personal medical histories Asthma Yes 10 12.2 [+ or -] 2.3 No 132 13.7 [+ or -] 0.8 Allergic rhinitis Yes 44 11.0 [+ or -] 0.9 No 98 14.8 [+ or -] 0.9 Adjusted urinary arsenic (a) High ([greater than or equal to] 7.7 [micro]g/g creatinine) 71 14.8 [+ or -] 1.1 Low (< 7.7 [micro]g/g creatinine) 71 12.4 [+ or -] 0.9 Adjusted urinary chromium (a) High ([greater than or equal to] 2.0 [micro]g/g creatinine) 71 15.5 [+ or -] 1.3 Low (< 2.0 [micro]g/g creatinine) 71 11.6 [+ or -] 0.6 Adjusted urinary nickel (a) High ([greater than or equal to] 71 13.8 [+ or -] 1.2 4.1 [micro]g/g creatinine)] Low (< 4.1 [micro]g/g creatinine) 71 13.3 [+ or -] 0.8 Variable Median Range Total 11.7 (0.4-59.7) Elementary school Longgang 18.8 (3.9-59.7) ** Shalach 9.9 (0.4-22.1) Shuntian 11.6 (0.7-37.3) Sex Boys 12.0 (0.4-39.7) Girls 11.3 (2.5-59.7) Paternal education (years) > senior high school ([greater than or equal to] 12) 11.4 (2.5-33.0) < senior high school (< 12) 12.0 (0.4-59.7) Maternal education (years) > senior high school ([greater than or equal to] 12) 10.8 (0.8-31.3) * < senior high school (< 12) 13.0 (0.4-59.7) Parental occupation Industry 12.8 (0.7-59.7) Nonindustry 10.6 (0.4-33.0) Parental smoking status Yes 12.8 (0.7-37.3) (#) No 10.6 (0.4-59.7) Possible indoor pollutants Pet feeding Yes 11.1 (3.2-33.1) No 12.0 (0.4-59.7) Incense burning at home all day Yes 11.1 (0.4-59.7) No 13.5 (0.8-39.7) Home dampness Yes 12.0 (2.5-59.7) No 11.4 (0.4-39.7) Personal medical histories Asthma Yes 10.1 (5.2-25.1) No 11.9 (0.4-59.7) Allergic rhinitis Yes 9.9 (0.4-25.1) * No 12.3 (0.7-59.7) Adjusted urinary arsenic (a) High ([greater than or equal to] 7.7 [micro]g/g creatinine) 12.4 (0.4-59.7) (#) Low (< 7.7 [micro]g/g creatinine) 11.1 (0.7-39.7) Adjusted urinary chromium (a) High ([greater than or equal to] 2.0 [micro]g/g creatinine) 12.4 (0.4-59.7) (#) Low (< 2.0 [micro]g/g creatinine) 11.1 (3.1-24.5) Adjusted urinary nickel (a) High ([greater than or equal to] 11.4 (0.4-59.7) 4.1 [micro]g/g creatinine)] Low (< 4.1 [micro]g/g creatinine) 12.3 (0.7-39.7) (a) Cut points were determined according to medians of urinary creatinine-adjusted levels among all subjects. * 0.01 < p < 0.05; ** p < 0.01; (#) 0.05 < p < 0.10. Table 3. Multiple linear regression model between the level of urinary 8-OHdG and incorporated concentration of arsenic and chromium (n = 142). Model Significance Explained Component model parameter (SE) (p-value) variance (%) Maternal education (< senior high school vs. > senior high school) 2.8 (1.4) 0.05 34.7 Parental smoking status (yes vs. no) 1.0 (1.4) 0.47 2.2 Allergic rhinitis (yes vs. no) -3.0 (1.6) 0.05 24.1 Adjusted urinary arsenic (high vs. low) (a) 1.9 (l.4) 0.18 17.5 Adjusted urinary chromium (high vs. low) (a) 3.0 (1.4) 0.04 21.5 (a) Cut points were determined according to medians (arsenic, 7.7 [micro]g/g creatinine; chromium, 2.0 [micro]g/g creatinine) of urinary creatinine-adjusted levels among all subjects.