Light-induced chromatid damage in human skin fibroblasts in culture in relation to their neoplastic potential.
Skin fibroblasts from ataxia telangiectasia and xeroderma pigmentosum (XP) donors and from the XP sib (possible heterozygote), all genetically predisposed to a high risk of cancer, show an increased susceptibility to light-induced chromatid breaks after culture in vitro. Light-induced chromatid breaks were shown previously to result from generation of hydrogen peroxide (H2O2) during light exposure. The level of susceptibility attained is significantly higher than that observed in 13 lines of fibroblasts from normal skin of donors ranging in age from 3 days to 92 years or from fetal skin tested at various population doubling levels. Two lines of normal skin fibroblasts transformed by chemical carcinogens to neoplastic cells also show a significant increase in susceptibility as compared with their untransformed controls. These data indicate for human cells, as reported earlier for mouse cells, an association between enhanced susceptibility to light-induced chromatid damage and neoplastic potential; this association is further supported by the high susceptibility of cells derived from a human adenocarcinoma. Two observations are consistent with the concept that the increased susceptibility does not result from greater initial damage to the DNA of the neoplastic cells. First, activities of the ubiquitous H2O2 scavenging enzyme, glutathione peroxidase, are similar in the paired normal and neoplastic cell populations. Second, cells of the paired lines are equally sensitive to DNA breakage by exogenous H2O2. The enhanced susceptibility associated with neoplastic potential may result from an impaired capacity to repair DNA rather than a greater initial sensitivity of the neoplastic cells to the damaging agent.
D000328:Adult; D000368:Aged; D001260:Ataxia Telangiectasia / Q000235:genetics*; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002648:Child; D002675:Child, Preschool; D002842:Chromatids / Q000187:drug effects / Q000528:radiation effects*; D004260:DNA Repair; D005260:Female; D005347:Fibroblasts / Q000528:radiation effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007231:Infant, Newborn; D008027:Light / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D012867:Skin / Q000201:enzymology / Q000528:radiation effects*; D014983:Xeroderma Pigmentosum / Q000235:genetics*
D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase