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Virus-smoking synergy causes malignancy.

Virus-smoking synergy causes malignancy

A sexually transmitted virus and a carcinogen found in tabacco smoke apparently join forces to cause mouse malignancies that resemble human cervical cancer, according to early results from an ongoing laboratory study

The research may eventually yield the first laboratory model of human cervical cancer, giving scientists a long-awaited glimpse into the cellular transformation that leads to the dealy disease, says Randall E. Harris, an epidemiologist at Ohio State University in Columbus.

Cervical cancer kills approximately 4,500 women in the United States each year. While epidemiologic studies have suggested a link with cigarette smoking (SN: 3/18/89, p.166), some scientists believe smoking alone does not heighten the risk of developing the disease. They point to research indicating that only smokers infected with certain types of human papillomavirus (HPV) show an increased incidence of cervical cancer.

A team led by Lenora R. Garrett at the Fred Hutchinson Cancer Research Center in Seattle now presents the first demonstration that HPV and tobacco toxins can join together in a cancer-causing partnership. Garrett reported the group's preliminary data last week at the American Cancer Society's annual science writers' seminar in Phoenix, Ariz.

The researchers started by culturing normal epithelial cells obtained from human foreskin samples. These skin cells resemble the epithelial cells lining the cervix but are easier to grow in the laboratory, Garrett explains. The team inserted DNA from HPV-18 -- one of the papillomaviruses previously linked to cervical cancer in smokers -- into the epithelial cells and then doused those cells with low doses of N-nitrosomethylurea, a cancer-causing chemical derived from the nicotine in tobacco smoke. After 24 hours, they harvested the treated epithelial cells and injected them beneath the skin of mice.

Six weeks later, 20 of the 24 mice injected with the treated cells had developed malignant tumors resembling those of humans with cervical cancer. When the researchers removed and analyzed the tumors, they detected chromosome damage associated with the loss or inactivation of genes responsible for controlling normal cell growth, Garrett says.

Another group of 24 mice received epithelial cells treated with HPV-18 or N-nitrosomethylurea, but not both. None showed evidence of tumors during the six-week study.

Garrett and others speculate that a two-step process sets the stage for human cervical cancer. HPV delivers the first blow by causing epithelial cells to divide rapidly, she explains. These proliferating cells, though not invasive, will then progress to malignancy if exposed to a second insult -- in this case, the carcinogen from tobacco smoke, Garrett suggests.

The Seattle team now hopes to demonstrate the virus-smoking synergy in experiments with human cervical cells. The researchers recently took the first step toward that goal, Garret says, by getting human cervical cells to grow in a laboratory culture.
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Title Annotation:smoking and human papillomavirus infection appear to cause cervical cancer
Author:Fackelmann, Kathy A.
Publication:Science News
Date:Apr 6, 1991
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