Production of DNA strand breaks by N-nitrosodimethylamine and 2-amino-3-methylimidazo[4,5- f]quinoline in THLE cells expressing human CYP isoenzymes and inhibition by sulforaphane

Abstract

The production of DNA strand breaks by N-nitrosodimethylamine (NDMA) and 2-amino-3-methylimidazo[4,5- f]quinoline (IQ) has been observed in T5-2E1 (expressing human CYP2E1) and T5-1A2 (expressing human CYP1A2) human liver cells respectively, using the Comet assay. Responses were statistically significant ( P < 0.05) and concentration dependent (0.01–1 μg ml −1 NDMA and 0.1–10 μg ml −1 IQ) and were not observed in T5-neo cells devoid of cytochrome P450 activity. Sulforaphane (1-isothiocyanate-4-methylsulfinylbutane) (0.1–10 μM) gave a marked inhibition of DNA strand breakage by these carcinogens ( P < 0.05 linear regression). This was seen in the absence of cytotoxicity and in the absence of an inhibition of H 2O 2-induced DNA strand breakage. The ability of sulforaphane to inhibit both CYP2E1 and CYP1A2-mediated genotoxicity therefore is relevant to human isoforms of these enzymes and may contribute to a chemopreventative activity.