Chromium(III) and DNA Damage.

In their paper, "Chromium(III)-Induced 8-Hydroxydeoxyguanosine in DNA and Its Reduction by Antioxidants: Comparative Effects of Melatonin, Ascorbate, and Vitamin E," Qi et al. (1) reported on a cell-free system and confirmed results from other laboratories that Cr(III) may react with peroxide to form reactive intermediates causing oxidative DNA damage. However, their conclusions on reactions in living systems are entirely speculative. Compounds of trivalent chromium are very weakly, if at all, carcinogenic (2-6). The authors misled readers when they cited Tsou et al. (7) and Lloyd et al. (8) as evidence for "the carcinogenic mechanisms of Cr(III)." The mechanism that Qi et al. (1) demonstrated by treating isolated DNA with Cr(III) plus 0.5 mM hydrogen peroxide does not apply to cells with a peroxide concentration of [10.sup.-9]-[10.sup.-8] M, but it does apply to cells that are subject to inflammation or other stress conditions in which the peroxide levels are increased. Nevertheless, the results of Qi et al. (1) should be taken as a warning that chromium(III) may be more harmful to living cells than thought previously, if it acts in combination with agents that cause the generation of reactive oxygen species. However, I question the final recommendation of the authors that melatonin should be applied against Cr-induced genotoxicity for two reasons: a) the supreme goal should be to avoid exposure to toxic chromium exposure, and b) reducing agents combined with Cr(VI) may create similar toxic intermediate oxidation states of Cr as does the oxidation of Cr(III) (9).

Detmar Beyersmann
Department of Biology and Chemistry
University of Bremen
Bremen, Germany
E-mail: [e-mail]

REFERENCES AND NOTES

(1.) Qi W, Reiter RJ, Tan D-X, Garcia JJ, Manchester LC, Karbownik M, Calvo JR. Chromium(III)-induced 8-hydroxy-deoxyguanosine in DNA and its reduction by antioxidants: comparative effects of melatonin, ascorbate, and vitamin E. Environ Health Perspect 108:399-402 (2000).

(2.) IARC. Chromium, Nickel and Welding. IARC Monogr Eval Carcinog Risks Hum 49:257-445 (1990).

(3.) Anttila S. Biological effects of occupational and environmental exposure to chromium. In: Metal Ions in Biology and Medicine (Collery P, ed). London:John Libbey, 1990;315-319.

(4.) Langard S. One hundred years of chromium and cancer: a review of epidemiological evidence and selected case reports. Am J Ind Med 17:189-215 (1990).

(5.) Norseth T. The carcinogenicity of chromium and its salts. Br J Ind Med 43:649-651 (1986).

(6.) Leonard A, Lawerys RR. Carcinogenicity and mutagenicity of chromium. Mutat Res 76:227-239 (1980).

(7.) Tsou T-C, Chen C-L, Liu T-Y, Yang J-L. Induction of 8-hydroxydeoxyguanosione in DNA by chromium(III) plus hydrogen peroxide and its prevention by scavengers. Carcinogenesis 17:103-108 (1996).

(8.) Lloyd DR, Carmichael PL, Phillips DH. Comparison of the formation of 8-hydroxy-2-deoxyguanosione and single- and double-strand breaks in BNA mediated by Fenton reaction. Chem Res Toxicol 11:420-427 (1998).

(9.) Kortenkamp A, Oetken G, Beyersmann D. The DNA cleavage induced by a chromium (V) complex and by chromate and glutathione is mediated by activated oxygen species. Mutat Res 232:155-161 (1991).