Sudman P D, Rutledge J C, Bishop J B, Generoso W M
Biology Division, Oak Ridge National Laboratory, TN 37831-8077, USA.
Mutat Res. 1992 Dec;296(1-2):143-56. doi: 10.1016/0165-1110(92)90038-b.
Limited comparative data in mice indicate that chemical mutagens that induce dominant lethal mutations in males are not necessarily effective in females, but those which are effective in females are generally equally or more effective in males. Recently, however, a few chemicals have been identified that are female-specific with respect to induction of dominant lethal mutations. The antitumor antibiotic adriamycin is among them. Another antitumor antibiotic, bleomycin was examined for its ability to induce dominant lethal mutations in the reproductive cells of male and female mice. No dominant lethal or cytotoxic effects were observed in males treated with bleomycin, even at a maximum tolerated dose. In females, on the other hand, a dose nearly 1/4 of that used in males induced not only a high level of dominant lethal mutations but also killed oocytes in certain stages of follicular development. The effectiveness of bleomycin in inducing dominant lethal mutations in mouse oocytes makes it a valuable tool for investigating whether gonadal transport, inherent differences in the configuration of chromatin in the germ cells of the two sexes or other factors are responsible for the differential susceptibility to bleomycin, which implies potential gender-specific genetic risk in cancer chemotherapy.
小鼠中的有限比较数据表明，在雄性中诱导显性致死突变的化学诱变剂在雌性中不一定有效，但在雌性中有效的那些通常在雄性中同样有效或更有效。然而，最近已经鉴定出一些在诱导显性致死突变方面具有雌性特异性的化学物质。抗肿瘤抗生素阿霉素就是其中之一。另一种抗肿瘤抗生素博来霉素被检测了其在雄性和雌性小鼠生殖细胞中诱导显性致死突变的能力。在用博来霉素处理的雄性小鼠中，即使在最大耐受剂量下，也未观察到显性致死或细胞毒性作用。另一方面，在雌性小鼠中，使用的剂量接近雄性所用剂量的1/4时，不仅诱导了高水平的显性致死突变，还杀死了卵泡发育某些阶段的卵母细胞。博来霉素在诱导小鼠卵母细胞显性致死突变方面的有效性使其成为一种有价值的工具，可用于研究性腺转运、两性生殖细胞中染色质构型的固有差异或其他因素是否导致对博来霉素的易感性差异，这意味着在癌症化疗中存在潜在的性别特异性遗传风险。
