Key Laboratory of Environmental Remediation and Ecological Health MOE, College of Environmental and Resource Sciences, Zhejiang University, No. 388, Yuhangtang Road, Hangzhou 310058, China; China Nuclear Power Engineering Co., Ltd, Beijing 100840, China.
Key Laboratory of Environmental Remediation and Ecological Health MOE, College of Environmental and Resource Sciences, Zhejiang University, No. 388, Yuhangtang Road, Hangzhou 310058, China.
Ecotoxicol Environ Saf. 2018 Mar;149:10-18. doi: 10.1016/j.ecoenv.2017.10.065. Epub 2017 Nov 13.
Although enantioselective accumulation of chiral pesticide has been reported in organisms, the mechanisms remain unclear. In this study, the effects of chiral pesticide metalaxyl on CYP1A1, CYP1A2, CYP2B1, CYP2B2, CYP2E1 and CYP3A were investigated in human hepatoma HepG2, rat hepatic H4IIE, chicken hepatic LMH and grass carp hepatic L8824 cells. Moreover, the residual concentrations and enantiomeric ratios (ERs) of metalaxyl were also detected in the medium. The results showed the responses of these CYP450s to metalaxyl were enzyme-dependent and species-dependent in the four cells. CYP1A1, CYP1A2, and CYP2B1 were induced in HepG2 cells, CYP2A1 and CYP2B1 were induced in H4IIE cells, CYP1A1 and CYP2B1 were induced in LMH cells, and CYP2B1 was induced in L8824 cells. The enantioselective residual of metalaxyl was detected in the medium and found to be species-specific. HepG2, H4IIE and LMH cells were inclined to attenuate S-metalaxyl and lead to decrease of ER of metalaxyl, while L8824 cells were inclined to remove R-metalaxyl and resulted in an inverse shift of ER. These findings suggest an enantioselective metabolism of metalaxyl in various species which is not only related with CYP450s and CYP450 enzyme-specific, but also species-specific.
尽管已有报道称手性农药在生物体中会发生对映体选择性积累，但其中的机制仍不清楚。本研究在人肝癌 HepG2 细胞、大鼠肝 H4IIE 细胞、鸡肝 LMH 细胞和草鱼肝 L8824 细胞中，研究了手性农药金属axyl 对 CYP1A1、CYP1A2、CYP2B1、CYP2B2、CYP2E1 和 CYP3A 的影响。此外，还检测了介质中金属axyl 的残留浓度和对映体比率（ER）。结果表明，四种细胞中金属axyl 对这些 CYP450 的反应具有酶依赖性和物种依赖性。CYP1A1、CYP1A2 和 CYP2B1 在 HepG2 细胞中被诱导，CYP2A1 和 CYP2B1 在 H4IIE 细胞中被诱导，CYP1A1 和 CYP2B1 在 LMH 细胞中被诱导，而 CYP2B1 在 L8824 细胞中被诱导。在介质中检测到金属axyl 的对映体选择性残留，发现其具有物种特异性。HepG2、H4IIE 和 LMH 细胞倾向于减弱 S-金属axyl，并导致金属axyl 的 ER 降低，而 L8824 细胞则倾向于去除 R-金属axyl，并导致 ER 发生反转。这些发现表明金属axyl 在不同物种中的对映体选择性代谢不仅与 CYP450 及其酶特异性有关，而且还具有物种特异性。
