The mutagenic potential of antiestrogens at the HPRT locus in V79 cells.

Tamoxifen, a nonsteroidal antiestrogen is widely used in the treatment of breast cancer. Although clearly of clinical value, it produces adverse side effects associated with its estrogen agonist activity. This has led to the development of antiestrogens with less estrogen agonist activity. Analog II (1,1-dichloro-cis-2,3-diaryl cyclopropane) is a cyclopropyl compound which produces pure antiestrogenic activity in mice and inhibits the proliferation of breast cancer cells. Since the genotoxicity of Analog II has not been examined, the aim of the present study was to investigate the mutagenic potential of Analog II. The mutagenic effects of Analog II were studied at the hypoxanthine phosphoribosyl transferase (hprt) locus in Chinese hamster lung fibroblasts (V79 cell line) and compared to tamoxifen and estradiol. In this study Analog II was not mutagenic at the hprt locus in V79 cells and appeared to have less mutagenic potential than either estradiol or tamoxifen. However, an examination of the genotoxicity of metabolic products of these compounds will be necessary before definite conclusions can be drawn concerning their genotoxicity in vivo.