potassium-bromate and Skin-Neoplasms

Xeroderma pigmentosum (XP) C is involved in the recognition of a variety of bulky DNA-distorting lesions in nucleotide excision repair. Here, we show that XPC plays an unexpected and multifaceted role in cell protection from oxidative DNA damage. XP-C primary keratinocytes and fibroblasts are hypersensitive to the killing effects of DNA-oxidizing agents and this effect is reverted by expression of wild-type XPC. Upon oxidant exposure, XP-C primary keratinocytes and fibroblasts accumulate 8,5'-cyclopurine 2'-deoxynucleosides in their DNA, indicating that XPC is involved in their removal. In the absence of XPC, a decrease in the repair rate of 8-hydroxyguanine (8-OH-Gua) is also observed. We demonstrate that XPC-HR23B complex acts as cofactor in base excision repair of 8-OH-Gua, by stimulating the activity of its specific DNA glycosylase OGG1. In vitro experiments suggest that the mechanism involved is a combination of increased loading and turnover of OGG1 by XPC-HR23B complex. The accumulation of endogenous oxidative DNA damage might contribute to increased skin cancer risk and account for internal cancers reported for XP-C patients.

Topics: Bromates; Cells, Cultured; DNA Damage; DNA Glycosylases; DNA Repair; DNA Repair Enzymes; DNA-Binding Proteins; Guanine; Humans; Keratinocytes; Oxidants; Skin Neoplasms; X-Rays; Xeroderma Pigmentosum

Six oxidizing chemicals were tested for promoting and complete carcinogenic activities in skin carcinogenesis using female Sencar mice. In the promotion tests, the chemicals were applied twice a week for 51 weeks after initiation with dimethylbenzanthracene (DMBA). In the tests for complete carcinogenic activities, the chemicals alone were applied for 51 weeks. Benzoyl peroxide was found to be a potent promoter as reported previously. Moreover, possible complete carcinogenic action of this chemical was found in this study. Potential promoting effect was suspected in sodium chlorite. Potassium bromate, ammonium persulphate, hydrogen peroxide and sodium hypochlorite were inactive either as a promoter or a complete carcinogen.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Animals; Benzoyl Peroxide; Bromates; Chlorides; Female; Hydrogen Peroxide; Mice; Oxidation-Reduction; Skin Neoplasms; Sodium Hypochlorite; Tetradecanoylphorbol Acetate