Chellman G J, Hurtt M E, Bus J S, Working P K
Department of Biochemical Toxicology, Chemical Industry Institute of Toxicology, Research Triangle Park, North Carolina.
Reprod Toxicol. 1987;1(1):25-35. doi: 10.1016/0890-6238(87)90068-2.
Exposure of male Fischer-344 (F-344) rats to methyl chloride (MeCl) results in testicular and epididymal toxicity and the induction of both pre- and postimplantation embryonic loss; the preimplantation loss is caused by cytotoxic damage to sperm that leads to failure of fertilization (Toxicol Appl Pharmacol 1986; 86:124-130). The present study examined whether the cytotoxicity of MeCl to sperm is due to the testicular or epididymal toxicity of MeCl. Groups of 18 males were exposed to 3000 ppm MeCl 6 h/day for 5 days, with and without concurrent treatment with the anti-inflammatory agent 3-amino-1-[m-(trifluoromethyl)phenyl]-2-pyrazoline (BW755C; 10 mg/kg, i.p. 1 h pre- and postexposure); BW755C was used to inhibit the epididymal toxicity of MeCl. Control groups were untreated or injected as described above with BW755C. Six males from each group were killed weekly for 3 weeks. Toxic effects of MeCl on the testis were demonstrated by decreased relative organ weight (week 3), testicular histopathology (weeks 1-3) and decreased daily sperm production (weeks 1-3); these effects were not prevented by BW755C. In both the MeCl and the MeCl + BW755C treatment groups, tubules devoid of sperm were observed in regions 4 and 5 of the epididymis at week 2, and in regions 6A and 6B at week 3. Sperm were present in the vas deferens of both groups at week 3 in decreased numbers and had decreased motility and more frequent morphologic abnormalities compared to untreated controls. In conjunction with known epididymal transit times for F-344 rat sperm, these data indicate that the induction of preimplantation loss by MeCl at weeks 2 and 3 postexposure is likely to result from cytotoxic effects on sperm located in the testes at the time of exposure.
将雄性Fischer-344（F-344）大鼠暴露于氯甲烷（MeCl）会导致睾丸和附睾毒性，并引发植入前和植入后胚胎丢失；植入前丢失是由精子的细胞毒性损伤导致受精失败引起的（《毒理学与应用药理学》1986年；86:124 - 130）。本研究考察了MeCl对精子的细胞毒性是否归因于MeCl的睾丸或附睾毒性。将18只雄性大鼠分为几组，每天6小时暴露于3000 ppm MeCl，持续5天，同时或不同时用抗炎剂3 - 氨基 - 1 - [间 - （三氟甲基）苯基] - 2 - 吡唑啉（BW755C；10 mg/kg，暴露前和暴露后1小时腹腔注射）进行处理；BW755C用于抑制MeCl的附睾毒性。对照组未进行处理或按上述方式注射BW755C。每组每周处死6只雄性大鼠，持续3周。MeCl对睾丸的毒性作用表现为相对器官重量降低（第3周）、睾丸组织病理学改变（第1 - 3周）以及每日精子生成量减少（第1 - 3周）；这些作用未被BW755C阻止。在第2周，MeCl处理组和MeCl + BW755C处理组的附睾4区和5区均观察到无精子的小管，在第3周，6A区和6B区也观察到无精子的小管。第3周时，两组大鼠输精管中的精子数量均减少，与未处理的对照组相比，精子活力降低且形态异常更为频繁。结合已知的F - 344大鼠精子在附睾中的转运时间，这些数据表明，暴露后第2周和第3周MeCl诱导的植入前丢失可能是由于暴露时睾丸中精子受到细胞毒性作用所致。
