Abnormal sensitivity of human fibroblasts from xeroderma pigmentosum variants to transformation to anchorage independence by ultraviolet radiation.

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.