Department of Biochemistry and Molecular Biology, Pondicherry University, India.
Chem Biol Interact. 2010 Apr 29;185(2):110-8. doi: 10.1016/j.cbi.2010.03.014. Epub 2010 Mar 12.
In the past few years, there has been much concern about the adverse health effects of environmental contaminants in general and organochlorine in particular. Studies have shown the repro-toxic effects of long-term exposure to methoxychlor, a member of the organochlorine family. However, the insight into the mechanisms of gonadal toxicity induced by methoxychlor is not well known. In the present study we sought to elucidate the mechanism(s) underpinning the gonadal effects within hours of exposure to methoxychlor. Experimental rats were divided into six groups of four each. Animals were orally administered with a single dose of methoxychlor (50mg/kg body weight) and killed at 0, 3, 6, 12, 24, and 72h post-treatment. The levels and time-course of induction of apoptosis-related proteins like cytochorome C, caspase 3 and procaspase 9, Fas-FasL and NF-kappaB were determined to assess sequential induction of apoptosis in the rat testis. DNA damage was assessed by TUNEL assay and flowcytometry. Administration of methoxychlor resulted in a significant increase in the levels of cytosolic cytochrome c and procaspase 9 as early as 6h following exposure. Time-dependent elevations in the levels of Fas, FasL, pro- and cleaved caspase 3 were observed. The DNA damage was measured and showed time-dependent increase in the TUNEL positive cells, and also by flowcytometry of testicular cells. The study demonstrates induction of testicular apoptosis in adult rats following exposure to a single dose of methoxychlor.
在过去的几年中，人们普遍关注环境污染物，特别是有机氯化合物对健康的不良影响。研究表明，长期接触甲氧滴滴涕（一种有机氯家族成员）会产生生殖毒性。然而，对于甲氧滴滴涕引起的性腺毒性的机制尚不清楚。在本研究中，我们试图阐明暴露于甲氧滴滴涕后数小时内引发性腺毒性的机制。实验大鼠分为六组，每组四只。动物经口给予甲氧滴滴涕（50mg/kg 体重），并在给药后 0、3、6、12、24 和 72 小时处死。测定细胞色素 C、半胱天冬酶 3 和前半胱天冬酶 9、Fas-FasL 和 NF-kappaB 等与凋亡相关的蛋白的水平和时间进程，以评估大鼠睾丸中凋亡的顺序诱导。通过 TUNEL 检测和流式细胞术评估 DNA 损伤。甲氧滴滴涕给药后 6 小时，细胞浆细胞色素 c 和前半胱天冬酶 9 的水平显著增加，表明 DNA 损伤。随着时间的推移，Fas、FasL、前半胱天冬酶 3 和半胱天冬酶 3 的水平逐渐升高。测量 DNA 损伤，显示 TUNEL 阳性细胞的时间依赖性增加，也通过睾丸细胞的流式细胞术显示。该研究表明，成年大鼠单次接触甲氧滴滴涕后会引发睾丸细胞凋亡。
