Rajah T T, Pento J T
Department of Pharmacology and Toxicology, College of Pharmacy, University of Oklahoma Health Sciences Center Oklahoma City 73190, USA.
Res Commun Mol Pathol Pharmacol. 1995 Jul;89(1):85-92.
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.
他莫昔芬是一种非甾体类抗雌激素药物，广泛应用于乳腺癌治疗。尽管其具有明确的临床价值，但会产生与其雌激素激动剂活性相关的不良副作用。这促使人们研发雌激素激动剂活性较低的抗雌激素药物。类似物II（1,1 - 二氯 - 顺式 - 2,3 - 二芳基环丙烷）是一种环丙基化合物，在小鼠体内具有纯抗雌激素活性，并能抑制乳腺癌细胞的增殖。由于尚未检测类似物II的遗传毒性，本研究的目的是探究类似物II的诱变潜力。在中国仓鼠肺成纤维细胞（V79细胞系）的次黄嘌呤磷酸核糖基转移酶（hprt）位点研究了类似物II的诱变作用，并与他莫昔芬和雌二醇进行比较。在本研究中，类似物II在V79细胞的hprt位点不具有诱变性，并且其诱变潜力似乎低于雌二醇或他莫昔芬。然而，在就这些化合物在体内的遗传毒性得出明确结论之前，有必要对其代谢产物的遗传毒性进行检测。
