Cellular responses to hematoporphyrin-induced photooxidative damage in Fanconi anemia, xeroderma pigmentosum and normal human fibroblasts.
Several observations reported in the literature suggest that singlet oxygen (1O2) might play a role in the clastogenic process in Fanconi anemia (FA) cells, and that the antioxidant status of xeroderma pigmentosum (XP) may also be altered. In order to test the ability of FA and XP cells, relative to normal cells, to cope with 1O2 damage, the effects of photosensitization by hematoporphyrin (HP) have been determined (i) on host cell reactivation (HCR) of damaged infecting herpes simplex virus (HSV) or transfecting SV40 DNA, and (ii) on DNA template capability and clonogenicity of treated cells. Results showed no significant difference among the three types of cells, either for the survival of HP-photosensitized HSV, or for the yields of SV40 virus following transfection of cultures with damaged viral DNA. The treatment of cells with HP plus 365-nm light leads to a dose-dependent, homothetic reduction of 18S and 28S ribosomal RNA (rRNA) synthesis, presumably through a mechanism other than the formation of transcription termination sites. After a 24-h post-exposure incubation, the rate of rRNA synthesis was restored to higher than normal levels in all cell lines. Finally, two FA cell lines showed a higher survival to HP photosensitization than two normal cell lines. Another FA cell line and XP-A and XP-C cells were in the range of sensitivity of the two normal strains for this treatment. These results indicate that FA cells possess an antioxidant defense system at least as efficient as that of normal cells for processing 1O2-induced damage.
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D043382:DNA-Formamidopyrimidine Glycosylase; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D005199:Fanconi Anemia / Q000188:drug therapy / Q000235:genetics*; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D006414:Hematoporphyrin Photoradiation; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D009699:N-Glycosyl Hydrolases / Q000378:metabolism; D012337:RNA, Ribosomal, 18S / Q000096:biosynthesis; D012339:RNA, Ribosomal, 28S / Q000096:biosynthesis; D013539:Simian virus 40 / Q000235:genetics; D018139:Simplexvirus / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection; D014983:Xeroderma Pigmentosum / Q000188:drug therapy / Q000235:genetics*
D012337:RNA, Ribosomal, 18S; D012339:RNA, Ribosomal, 28S; D016685:Mitomycin; D009699:N-Glycosyl Hydrolases; D043382:DNA-Formamidopyrimidine Glycosylase