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). AdCA 17 is non-replicating recombinant human adenovirus that infects human cells and expresses the P-galactosidase (P-gal) reporter gene. We have examined host cell reactivation (HCR) of beta-gal activity for (NIB + VL)-treated AdCA 17 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 NIB + VL-treated reporter gene giving evidence for a UVC-inducible and XPC-independent BER pathway in human cells. (c) 2007 Elsevier Inc. All rights reserved.