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Carcinogenesis Laboratory, Department of Microbiology and Department of Biochemistry, Michigan State University, East Lansing, Michigan 48824-1316
One class of xeroderma pigmentosum (XP) patients, known as XP variants, inherit the characteristic predisposition to sunlight-induced skin cancer, but unlike the majority of XP patients, their cells do not exhibit a deficiency in rate of excision repair of ultraviolet (UV) radiation-induced DNA damage. XP variant cells are only slightly more sensitive than normal to killing by 254 nm UV radiation or simulated sunlight. But they are much more sensitive than normal to the induction of mutations by these agents. We investigated their sensitivity to UV-induced transformation to anchorage independence compared to that of normal cells. Low doses of UV (2 to 4.5 J/m2), doses which resulted in little or no measurable transformation in normal cells, caused a dose-dependent increase in the frequency of anchorage independent XP variant cells. Doses of 6 to 8 J/m3 were required to elicit a comparable response in the normal fibroblasts. Even when the two kinds of cells were compared at doses adjusted to give equal cytotoxicity, the frequency of transformation in the XP variant cells was higher than normal. Thus, their sensitivity to induction of anchorage independence by UV paralleled their sensitivity to UV-induced mutations.
1 This research was supported in part by Department of Health and Human Services, NIH Grants CA 21289 and CA21253 from the National Cancer Institute, by Department of Energy Contract EV-4659, and by a grant from the Women's Auxiliary of the Veterans of Foreign Wars.
2 Present address: Division of Radiation Biology, Kanazawa University, Kanazawa, Japan.
3 To whom requests for reprints should be addressed, at Carcinogenesis Laboratory, Fee Hall, Michigan State University, East Lansing, MI 48824-1316.
Received 8/ 9/85. Revised 10/24/85. Accepted 10/25/85.
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