INTERACTION OF ARSENIC(III) WITH NUCLEOTIDE EXCISION-REPAIR IN UV-IRRADIATED HUMAN FIBROBLASTS

Even though epidemiological studies have identified arsenic compounds as carcinogenic to humans, they are not mutagenic in bacterial and mam malian test systems. However, they increase the mutagenicity and clast ogenicity in combination with other DNA damaging agents and there are indications of inhibition of DNA repair processes, We investigated the effect of arsenic(III) on nucleotide excision repair (NER) after UV i rradiation in human fibroblasts in detail by using two repair-proficie nt and one partly repair-deficient xeroderma pigmentosum group C human fibroblast cell lines, The results show that two steps of NER are aff ected by arsenite, Most severely, the incision frequency is reduced at concentrations as low as 2.5 mu M arsenic(III); at higher, cytotoxic concentrations, the ligation of repair patches is also impaired, Furth ermore, our results indicate that both the global genome repair pathwa y and the transcription-coupled repair pathway are affected by arsenit e, Repair inhibition may well explain the potentiation of genotoxic ef fects by arsenic in combination with other DNA damaging agents and may thus be of high relevance for the carcinogenic action of arsenic comp ounds.