ATLA::Alternatives to Laboratory Animals

Volume 24, Number 4

DT-diaphorase affects the mutagenic activity of pyrene 1,6-quinon in Chinese hamster epithelial liver (CHEL) cells.

ATLA 24, 567-571, July/August 1996

Paola Rossini and Gino Turchi

ECVAM, JRC Environment Institute, 21020 Ispra (Va), Italy

SUMMARY

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 xenobioticmetabolising 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 DTdiaphorase. In V79 cells, dicoumarol (1001lM) 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 1,6Q to redox-stable hydroquinone.

Keywords: pyrene 1,6-quinone, DT-diaphorase, dicoumarol, epithelial liver cells, hgprt locus