Yegana Y, Zimber A, Perk K
Department of Animal Science, Hebrew University of Jersalem, Faculty of Agriculture, Rehovot, Israel.
Anticancer Res. 1988 May-Jun;8(3):397-401.
Single IP injection of high dose (LD 10) of methyl-CCNU administered to sexually mature male mice resulted in severe inhibition of spermatogenesis and reduction in testicular wet weight, without significant changes in plasma testosterone levels, and with hyperplasia of the interstitum, including Leydig cells, in the testis. These effects were temporary, spermatogenesis and testiculer weight recovered 50 days after treatment. Mating of the treated males with normal females demonstrated absolute sterility at 20 days and full recovery at 50 days after treatment. Administration of a single lethal dose (38 mg/kg, LD70) of methyl-CCNU to immature (25 day-old) male mice also caused severe but temporary inhibition of spermatogenesis, and mating of mice which survived the treatment and reached sexual maturity, with normal females, resulted in 80 to 100% pregnancies at 40 and 70 days after treatment, respectively. Three repeated injections of 30 mg/kg (at 10 day intervals) of methyl-CCNU to 15 day-old male mice resulted in inhibition of spermatogenesis without alteration in plasma testosterone. Ninety days after this treatment, only 40% of matings with normal females resulted in pregnancies. Female mice treated once with 20 mg/kg of methyl-CCNU, 3 days before or 7 days after mating with normal males, showed complete failure to complete pregnancy-resorption of the embryos was demonstrated in those female mice treated 7 days after mating. After a second mating trial with these two treated groups, performed 40 to 55 and 42 days after the first trial, respectively, 80 and 86% of the females delivered offspring. However, average litter size was reduced to 4 in the second group, as compared to 8 in untreated mice. There were no apparent birth defects in the offspring of methyl-CCNU treated male or female mice.
对性成熟雄性小鼠单次腹腔注射高剂量（半数致死量10）的甲基环己亚硝脲，会导致精子发生严重受抑，睾丸湿重减轻，血浆睾酮水平无显著变化，且睾丸间质包括睾丸间质细胞增生。这些影响是暂时的，治疗后50天精子发生和睾丸重量恢复。经治疗的雄性小鼠与正常雌性小鼠交配，在治疗后20天表现为绝对不育，50天完全恢复。对未成熟（25日龄）雄性小鼠单次给予致死剂量（38毫克/千克，半数致死量70）的甲基环己亚硝脲，也会导致精子发生严重但暂时受抑，存活并达到性成熟的小鼠与正常雌性小鼠交配，在治疗后40天和70天分别有80%至100%的受孕率。对15日龄雄性小鼠每隔10天重复注射3次30毫克/千克的甲基环己亚硝脲，会导致精子发生受抑，血浆睾酮无变化。治疗90天后，与正常雌性小鼠交配仅有40%受孕。在与正常雄性小鼠交配前3天或交配后7天，对雌性小鼠单次给予20毫克/千克的甲基环己亚硝脲，结果显示交配后7天接受治疗的雌性小鼠完全无法受孕，胚胎出现吸收。对这两个治疗组在首次试验后分别于40至55天和42天进行第二次交配试验，80%和86%的雌性小鼠产仔。然而，第二组的平均窝仔数降至4只，而未治疗小鼠为8只。甲基环己亚硝脲治疗的雄性或雌性小鼠后代无明显出生缺陷。
