DT-Diaphorase Affects the Mutagenic Activity of Pyrene 1,6-Quinone in Chinese Hamster Epithelial Liver (CHEL) Cells

Abstract

The mutagenic potential of pyrene 1,6-quinone (P 1,6-Q) has been studied in a wide range of in vitro genetic assays including the use of mammalian cell lines. P 1,6-Q has been shown to induce gene mutations and micronuclei in V79 cells, whereas, in Chinese hamster epithelial liver (CHEL) cells, a cell line which retains activities of various xenobiotic-metabolising enzymes, a non-specific pattern of structural and numerical chromosomal aberrations has been observed. In this study, we have evaluated the mutagenic activity of P 1,6-Q on V79 and CHEL cells both with and without dicoumarol, a potent inhibitor of DT-diaphorase. In V79 cells, dicoumarol (100μM) did not affect the mutagenic response, whereas in CHEL cells, the mutation frequency significantly increased. This suggests that DT-diaphorase, which is expressed in liver cells at high levels, has a possible role in the detoxification of P 1,6-Q to redox-stable hydroquinone.