Biotransformation enzyme-dependent formation of micronucleus and multinuclei in cell line V79-hCYP2E1-hSULT1A1 by 2-nitropropane and N-nitrosodimethylamine

V79-hCYP2E1-hSULT1A1, a V79-derived cell line co-expressing both human CYP2E1 and SULT1A1, has been constructed and efficiently used in detection of the mutagenic activities of a number of promutagens. 2-Nitropropane (2-NP) and N-nitrosodimethylamine (NDMA), both being hepatocarcinogenic to animals but inactive in standard genotoxicity assays in vitro, are activated to mutagenic metabolites by human SULT1A1 and CYP2E1, respectively. Nevertheless, little is known about the chromosomal effects of these two carcinogens. In the present study, we investigated the effects of 2-NP and NDMA on frequencies of micronucleated (Fmi) and multinucleated cells (Fmu) in V79-hCYP2E1-hSULT1A1 cells. The results showed induction of both Fmi and Fmu by 2-NP and NDMA individually, and this effect was completely suppressed by relatively specific inhibitor of SULT1A1 and CYP2E1, i.e., pentachlorophenol and 1-aminobenzotriazole, respectively. The Fmu/Fmi ratio in 2-NP groups was significantly higher than NDMA groups, probably indicating an aneugenic activity of 2-NP based on proposed Fmu/Fmi ratio as a simple index to discriminate aneugens from clastogens. The present study has established biotransformation enzyme-dependent formation of multinuclei and micronuclei induced by 2-NP and NDMA.

► Micronuclei and multinuclei induced by N-nitrosodimethylamine and 2-nitropropane. ► Human CYP2E1-dependent activation of N-nitrosodimethylamine. ► Human sulfotransferase 1A1-dependent activation of 2-nitropropane.