Developmental Toxicology Division, CSIR-Indian Institute of Toxicology Research, P.O. Box 80, M.G. Marg, Lucknow 226 001, UP, India.
Food Chem Toxicol. 2013 Oct;60:318-27. doi: 10.1016/j.fct.2013.07.049. Epub 2013 Aug 6.
Studies were initiated to investigate the similarities in alterations in cytochrome P450s (CYPs) and associated signaling events in brain and peripheral blood lymphocytes (PBL) induced by lindane, an organochlorine pesticide. Adult male albino wistar rats were treated orally with different doses (2.5- or 5.0- or 10- or 15 mg/kg/body weight) of lindane daily for 4 days. In another experiment, the treatment of low dose (2.5mg/kg) of lindane was continued for 15- and 21 days. A dose- and time-dependent increase was observed in the activity of CYP dependent enzymes in brain microsomes and PBL isolated from the treated rats. However, the magnitude of induction was several folds less in PBL. As observed in brain, RT-PCR and Western immunoblotting demonstrated that increase in CYP enzymes in PBL is due to the increase in the mRNA expression of specific CYP isoenzymes. Similarities were also observed in activation of ERK and JNK MAP kinases and c-jun in PBL or brain isolated from rats treated with lindane. Similarities in the induction of CYPs and activation of MAP kinases in PBL and brain suggest that CYP expression profiles in PBL could be used for monitoring the exposure and toxicity of environmental chemicals.
研究旨在探讨林丹（一种有机氯杀虫剂）诱导的脑和外周血淋巴细胞（PBL）中细胞色素 P450（CYPs）改变和相关信号事件的相似性。成年雄性白化 Wistar 大鼠每天经口给予不同剂量（2.5 或 5.0 或 10 或 15mg/kg 体重）的林丹连续 4 天。在另一个实验中，继续用低剂量（2.5mg/kg）林丹处理 15 和 21 天。在脑微粒体和从处理大鼠中分离的 PBL 中观察到 CYP 依赖性酶的活性呈剂量和时间依赖性增加。然而，在 PBL 中的诱导幅度小几个数量级。与在脑中观察到的一样，RT-PCR 和 Western 免疫印迹表明 PBL 中 CYP 酶的增加是由于特定 CYP 同工酶的 mRNA 表达增加所致。用林丹处理的大鼠的 PBL 或脑分离物中 ERK 和 JNK MAP 激酶和 c-jun 的激活也观察到相似性。PBL 中 CYP 的诱导和 MAP 激酶的激活相似性表明，PBL 中的 CYP 表达谱可用于监测环境化学物质的暴露和毒性。
