Sex hormones and neoplasia: genotoxic effects in short term assays

The mechanism of the tumorigenic effects of sex hormones in the liver and in other organs is still unclear. Clues towards an understanding of this action of sex hormones can be gained from short-term assays suitable for revealing adverse effects at different molecular levels relevant to the process of neoplastic transformation. The available data on the effects of sex hormones indicating gene mutations, unscheduled DNA synthesis, sister chromatid exchange, chromosomal anomalies, induction of aneuploidy and cell transformation are reviewed. Although the data base is scant, in particular for androgens and progestins and in systems other than the mutational assays, it can be concluded that sex hormones, in general, fail to induce gene mutations. On the other hand, recent evidence shows that diethylstilbestrol and steroidal estrogens are capable of inducing neoplastic transformation in vitro. In this context, the induction of aneuploidy is discussed as non-mutational but genotoxic effect of estrogens responsible for the neoplastic transformation. Morphological transformation and scoring for chromosomal anomalies can provide useful endpoints for further evaluation of sex hormones with suspected carcinogenic properties.