Deficient base excision repair of oxidative DNA damage induced by methylene blue plus visible light in xeroderma pigmentosum group C fibroblasts.
Methylene blue plus visible light (MB+VL) results in oxidative DNA damage, producing predominantly 7,8-dihydroxy-8-oxoguanine and other single base modifications that are repaired by base excision repair (BER). AdCA17 is non-replicating recombinant human adenovirus that infects human cells and expresses the beta-galactosidase (beta-gal) reporter gene. We have examined host cell reactivation (HCR) of beta-gal activity for (MB+VL)-treated AdCA17 in cells from patients with xeoroderma pigmentosum from complementation group C (XP-C). HCR was substantially reduced in an SV40 transformed XP-C fibroblast compared to two SV40-transformed normal cells and in three XP-C primary fibroblast strains compared to four normal strains for both untreated and UVC-treated cells. These results indicate an involvement of the XPC gene in BER of MB+VL-induced oxidative DNA damage. In addition, pre-UVC-treatment of both normal and XP-C fibroblasts resulted in enhanced HCR of the MB+VL-treated reporter gene giving evidence for a UVC-inducible and XPC-independent BER pathway in human cells.
Kassam
Shaqil N
SN
Department of Biology, McMaster University, Hamilton, Ont., Canada L8S 4K1.
Rainbow
Andrew J
AJ
D002478:Cells, Cultured; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects*; D005347:Fibroblasts / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D008027:Light; D008751:Methylene Blue / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects*; D014983:Xeroderma Pigmentosum / Q000235:genetics* / Q000473:pathology*
D008751:Methylene Blue