INDUCTION OF SISTER CHROMATID EXCHANGE BY DIETHYLSTILBESTROL IN METABOLICALLY COMPETENT HEPATOMA-CELL LINES BUT NOT IN FIBROBLASTS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (9) , 3851-3855
Abstract
The effect of diethylstilbestrol (DES) on sister chromatid exchange (SCE) induction was measured in 4 cell lines to determine whether metabolic activation of DES is a factor in its genotoxic potential. Two of these, cell lines derived from a human hepatoblastoma (HepG2-GW) and a rat hepatoma (H4-AG), were shown previously to be capable of metabolizing several procarcinogens to their active forms. DES, in a dose range of 1 .times. 10-8 M-1 .times. 10-5 M, increased SCE frequencies by 50 to 60% in both the rat and human hepatoma lines but had no effect on SCE induction in Chinese hamster lung fibroblasts (V79-GW) or human diploid skin fibroblasts (MGH 2C-GW), both of which are nonmetabolizing cell lines. Furthermore, pretreatment of the responsive cell lines (H4-AG and HepG2-GW) with indomethacin, an inhibitor of prostaglandin synthetase-mediated metabolism of DES, effectively prevented the induction of SCE by DES. DES failed to increase the frequency of hypoxanthine-guanine phosphoribosyltransferase locus mutants in H4-AG cells, over a dose range which induced SCE. DES evidently induces SCE but does not induce gene mutation. Growing evidence that metabolic activation of DES may be an important factor in its genotoxic and carcinogenic mechanisms is supported.

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