Department of Environmental Health and Toxicology, Tokyo Metropolitan Institute of Public Health, Tokyo, Japan.
Food Chem Toxicol. 2011 Jan;49(1):49-56. doi: 10.1016/j.fct.2010.09.029. Epub 2010 Oct 12.
Rats and mice (8 animals per species per group) were injected subcutaneously or intraperitoneally with paradichlorobenzene (PDCB) at doses of 0, 100, 200 and 400 mg/kg/day, 4-5 days a week, for 8 weeks (for rats) and either 2 or 6 weeks (for mice). Prostate and seminal vesicle weights were significantly increased in PDCB-treated rats but not in mice. Major histopathologic injuries were not found in testis and epididymis of both species. Daily sperm production was depressed in both species in a dose-response manner. Serum testosterone levels were not significantly changed in both species. Sperm morphology was evaluated in rats intraperitoneally administered PDCB at a dose of 800 mg/kg. Abnormal sperms with reduced hook, bent neck, coiled flagellum, bent flagellum and bent flagellum tip were significantly increased in treated rats. In Hershberger assay, PDCB administration increased weights of ventral prostate gland, seminal vesicle, levator ani/bulbocavernosus muscle and glans penis in castrated rats, and also weights of ventral prostate gland and glans penis in castrated mice. PDCB and 2,5-dichlorophenol (the major metabolite) did not bind androgen receptor (AR) up to 10 mM. In conclusion, PDCB affects sperm production and morphology but is somewhat androgenic independently from AR binding in rats and mice.
雄性大鼠和小鼠(每组 8 只)每周接受 5 天皮下或腹腔注射 0、100、200 和 400mg/kg/d 的对二氯苯(PDCB),连续 8 周(大鼠)或 2 或 6 周(小鼠)。PDCB 处理的大鼠前列腺和精囊重量显著增加,但小鼠未增加。两种动物的睾丸和附睾组织学未见主要损伤。PDCB 处理的两种动物的精子生成均呈剂量依赖性抑制。两种动物的血清睾酮水平均无显著变化。大鼠腹腔注射 800mg/kg/d 的 PDCB 后评估精子形态。处理组的畸形精子(钩状减少、颈部弯曲、卷曲鞭毛、弯曲鞭毛和鞭毛尖端弯曲)显著增加。在 Hershberger 试验中,PDCB 给药增加去势大鼠的前列腺腹侧叶、精囊、会阴肌和阴茎龟头的重量,也增加去势小鼠的前列腺腹侧叶和龟头的重量。PDCB 和 2,5-二氯苯酚(主要代谢物)在 10mM 以内不与雄激素受体(AR)结合。总之,PDCB 影响大鼠和小鼠的精子生成和形态,但与 AR 结合无关,具有一定的雄激素作用。