Oxidative DNA damage by minor metabolites of toluene may lead to carcinogenesis and reproductive dysfunction

Recently, the concern that toluene might have carcinogenic and reproductive toxic potential has been raised. We investigated the ability of DNA damage by minor metabolites of toluene, methylhydroquinone, and methylbenzoquinone, using P-32-5'-end-labeled DNA fragments obtained from the human genes. Methylhydroquinone caused Cu(II)-mediated DNA damage, whereas methylbenzoquinone did only in the presence of NADH. DNA damage by methylbenzoquinone was weaker than that by benzoquinone, a metabolite of carcinogenic benzene. Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by metabolites of toluene increased with its concentration in the presence of Cu(II) and NADH. Generation of O-2(.-) and semiquinone radicals was detected by UV-visible and ESR spectroscopies, respectively. These results suggest that these metabolites may play some roles in expression of carcinogenicity and reproductive toxicity of toluene. We have discussed the differences of carcinogenic potency between toluene and benzene in relation to the amount of metabolites and their ability to damage DNA. (C) 1999 Academic Press.