Abnormal response of xeroderma pigmentosum cells to bleomycin

The repair of bleomycin-damaged DNA was examined in human fibroblasts isolated from patients having the disease xeroderma pigmentosum (XP). In normal fibroblasts, the appearance of low-molecular-weight DNA was observed in the presence of increasing amounts of the drug. The studies in XP fibroblasts produced results which differed from those obtained in normal cells in two ways. (a) Prelabeled XP cells from most complementation groups contained more low-molecular-weight DNA than observed in the other human fibroblasts examined. (b) When XP cells were exposed to low doses of bleomycin, the low-molecular-weight DNA disappeared, suggesting induction of a repair process. If the XP cells were exposed to bleomycin in the presence of hydroxyurea and 1-beta-D-arabinofuranosylcytosine, the disappearance of low-molecular-weight DNA was not observed; instead, a normal dose response to the drug was observed. Our results suggest that XP cells show an "induced" repair response following bleomycin treatment and that blocking DNA chain elongation uncovers normal incisions in bleomycin-treated DNA.