Differential effects of mercury compounds on mutagenicity, genotoxicity and repair of UV-DNA damage

Abstract

Mercury (Hg) is a global contaminant that is present in human diet as methylmercury (MeHg). Recent studies linked MeHg exposure with high risks of skin cancers. It is unknown whether MeHg is directly genotoxic in skin cells or able to enhance mutagenic effects of UV radiation. We examined mutagenicity and genotoxicity of MeHg and its metabolite inorganic Hg^2 + (iHg) and their impact on processing of carcinogenic UV-DNA damage. We found that iHg and MeHg were both nonmutagenic in the Hprt assay in rodent CHO cells. iHg but not MeHg strongly enhanced mutagenicity of UV-B without changes in repair of mutagenic cyclobutane pyrimidine dimers (CPDs). In human keratinocytes, iHg increased genotoxic stress and formation of micronuclei by UV-B which occurred in cells with both normal and inactive nucleotide excision repair of UV-DNA damage. Repair of UVB-induced CPDs and 6–4 photoproducts in keratinocytes was unaffected by iHg or MeHg. Formation of micronuclei in human keratinocytes by MeHg and UV-B was additive, indicating their independence. Thus, iHg(II) was not directly mutagenic/genotoxic but it enhanced mutagenicity and clastogenicity of UV-DNA damage without interference with its repair. MeHg did not alter DNA repair or mutagenicity/genotoxicity of UV-B but it acted as a clastogen in human keratinocytes.