Weber Lynn P, Kiparissis Yiannis, Hwang Gap S, Niimi Arthur J, Janz David M, Metcalfe Chris D
Department of Zoology, Oklahoma State University, 430 Life Sciences West, Stillwater, OK 74078, USA.
Comp Biochem Physiol C Toxicol Pharmacol. 2002 Jan;131(1):51-9. doi: 10.1016/s1532-0456(01)00276-9.
Increasing evidence suggests that sublethal effects of natural or xenobiotic chemicals in the environment may be mediated via the stimulation of apoptosis. To investigate whether apoptosis can be induced in fish by weakly estrogenic and androgenic chemicals, adult male Japanese medaka (Oryzias latipes) were exposed to 100 ppb of the estrogenic alkylphenol, 4-nonylphenol, and adult female medaka were exposed to 100 ppb of the aromatase-inhibiting bioflavonoid, quercetin, for 6 weeks. Exposure to nonylphenol and quercetin had no significant effect on the length, weight or condition factors compared to solvent (acetone) controls in male or female medaka. Apoptosis was evaluated in blinded histological sections of whole medaka using terminal dideoxynucleotidyl transferase dUTP nick end labeling (TUNEL) that labels nuclei of cells containing apoptotic (fragmented) DNA. There was a six-fold greater extent of apoptosis in spermatocytes, Sertoli cells and Leydig-homologue cells, but not in spermatids of testes from nonylphenol-exposed male medaka compared to testes of solvent controls. No significant differences in the extent of apoptosis were detected in intestine, liver or kidney from the same male fish. Quercetin-treated female medaka had a significantly increased number of atretic ovarian follicles, but no significant differences in the extent of apoptosis in intestine, liver or kidney. These results suggest that nonylphenol caused testicular degeneration via increased testicular cell apoptosis, while quercetin may be ovotoxic via increased follicular atresia.
越来越多的证据表明，环境中天然或外源性化学物质的亚致死效应可能是通过刺激细胞凋亡来介导的。为了研究弱雌激素和雄激素化学物质是否能诱导鱼类细胞凋亡，将成年雄性日本青鳉（Oryzias latipes）暴露于100 ppb的雌激素烷基酚4-壬基酚中，将成年雌性日本青鳉暴露于100 ppb的芳香化酶抑制生物类黄酮槲皮素中，持续6周。与雄性或雌性日本青鳉的溶剂（丙酮）对照组相比，暴露于壬基酚和槲皮素对鱼的体长、体重或状况因子没有显著影响。使用末端脱氧核苷酸转移酶dUTP缺口末端标记法（TUNEL）对整个青鳉的盲法组织切片进行细胞凋亡评估，该方法可标记含有凋亡（片段化）DNA的细胞核。与溶剂对照组的睾丸相比，暴露于壬基酚的雄性日本青鳉睾丸中的精母细胞、支持细胞和类Leydig细胞的凋亡程度高出六倍，但精子细胞中没有。在同一条雄鱼的肠道、肝脏或肾脏中未检测到凋亡程度的显著差异。经槲皮素处理的雌性日本青鳉闭锁卵泡数量显著增加，但在肠道、肝脏或肾脏中的凋亡程度没有显著差异。这些结果表明，壬基酚通过增加睾丸细胞凋亡导致睾丸退化，而槲皮素可能通过增加卵泡闭锁而具有卵巢毒性。
