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首页> 外文期刊>Journal of biochemical and molecular toxicology >Modulation of CPP32 activity and induction of apoptosis in Human CEM X 174 lymphocytes by heptachlor, a chlorinated hydrocarbon insecticide.
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Modulation of CPP32 activity and induction of apoptosis in Human CEM X 174 lymphocytes by heptachlor, a chlorinated hydrocarbon insecticide.

机译:七氯(一种氯化碳氢化合物杀虫剂)对CPP32活性的调节和对人CEM X 174淋巴细胞凋亡的诱导。

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摘要

Heptachlor is an organochlorine insecticide used worldwide for the control of pests both agriculturally and domestically. Its lipophilic structure allows it to bioaccumulate and pass through the food chain, exposing those who come in contact with it to its tumor promoting and possible carcinogenic effects. As a mechanism of tumor promotion, we explored the possibility of heptachlor suppressing the apoptotic process in human CEM x 174 lymphocytes. In this article, we describe the effect of heptachlor on the activity of the apoptosis protease CPP32. We show that heptachlor by itself was able to stimulate CPP32 activity at relatively high concentrations. When combined with the chemotherapeutic agent doxorubicin, a known CPP32 activator, a dual effect was observed. Low concentrations of heptachlor (5 microM-10 microM) suppressed doxorubicin-induced CPP32 activity, and high concentrations of heptachlor (80 microM-120 microM) augmented it. We also showed that heptachlor alone at relatively high concentrations induced apoptosis-associated changes in CEM x 174 cells including high molecular weight (HMW) DNA cleavage and chromatin condensation. From these results, it appears that heptachlor has tumor promoting-like effects at lower concentrations, and at higher concentrations induces apoptosis as a mechanism of cytotoxicity.
机译:七氯是一种有机氯杀虫剂,在世界范围内用于在农业和家庭内控制害虫。它的亲脂结构使它能够生物积累并穿过食物链,使与之接触的人暴露于促进肿瘤和可能的致癌作用。作为促进肿瘤的机制,我们探索了七氯抑制人CEM x 174淋巴细胞凋亡过程的可能性。在本文中,我们描述了七氯对细胞凋亡蛋白酶CPP32活性的影响。我们表明,七氯本身能够在相对较高的浓度下刺激CPP32的活性。当与已知的CPP32活化剂阿霉素联合使用时,观察到双重作用。低浓度的七氯(5 microM-10 microM)抑制了阿霉素诱导的CPP32活性,而高浓度的七氯(80 microM-120 microM)增强了它的活性。我们还显示,单独的相对较高浓度的七氯会在CEM x 174细胞中诱导凋亡相关变化,包括高分子量(HMW)DNA裂解和染色质浓缩。从这些结果来看,似乎七氯在较低浓度下具有肿瘤促进样作用,而在较高浓度下则诱导凋亡作为细胞毒性机制。

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