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  • The enantiomeric ratio ER of chiral compounds accumulated in


    The enantiomeric ratio (ER) of chiral compounds accumulated in organisms has been found to be different among species (Borga and Bidleman, 2005, Harner et al., 1999, Warner et al., 2005, Wiberg et al., 2000), indicating enantioselective accumulation of chiral compounds are species-specific. The ER of α-HCH was detected to vary along the polar bear food chain and increase from ≈1.0 in cod to 2.3 in polar bear (Wiberg et al., 2000). In arctic marine invertebrates, depletion of the (+)-α-HCH enantiomer increased from ice fauna to zooplankton, and to benthos (Borga and Bidleman, 2005, Harner et al., 1999). Compared to α-HCH, chlordane and o,p'-DDT showed stronger enantioselective bioaccumulation in benthic amphipods than in zooplankton and ice fauna (Borga and Bidleman, 2005). In the similar area, enantioselective species-specific biotransformation of individual PCB stereoisomers has also been reported in marine food web. Greater nonracemic enantiomeric fractions (EFs) of PCBs were observed in several seabird species and ringed seals, but racemic EFs were found in the prey such as zooplankton and fish (Warner et al., 2005). Besides in animals, the accumulation of chiral compounds has also been found to be enantioselective species-specific in plants (Wang et al., 2014, Schneiderheinze et al., 1999). However, the mechanisms of enantioselective species-specific biotransformation of chiral compounds have received little attention and remain unclear so far. Xenobiotic metabolism primarily occurs in liver, which contains many enzymes to catalyze the transformation of xenobiotic. Usually, cytochrome P-450s (CYP450s) act as the first response for biotransformation of xenobiotic in organisms. CYP450s generally consist of various subfamily enzymes which can catalyze different reactions of xenobiotic (Tang et al., 2006). Previous studies have revealed that the effects of a actin polymerization inhibitor varied among CYP450 enzymes, indicating that the effects of a compound on CYP450s were enzyme-specific. CYP450 enzyme-specific metabolism has been reported for some pollutants such as PCB, dioxins and other xenobiotics (Guengerich, 2001, Lu et al., 2013, Vijaya Padma et al., 2014). The findings suggest that a compound could be catalyzed by one or several specific CYP450 enzymes during its metabolism by CYP450s (Guengerich, 2008). Therefore, CYP450 enzyme-specific interaction with pollutants provides us to better understand the pathway of metabolism of pollutants. Metalaxyl is a chiral pesticide with a stereogenic center in the carboxy alkyl moiety, and thus consists of a pair of enantiomers (Fig. S1, Supporting Material). Since first introduced in 1977, metalaxyl has been widely used as a fungicide to control diseases caused by Oomycetes on a wide range of plants including crops for more than thirty years (Li et al., 2013, Monkiedje et al., 2003). With the wide application, metalaxyl has been detected in many environmental matrixes, including water, soil, and sediment as well as organisms (Martin et al., 2012, Monkiedje et al., 2003, Sanchez-Gonzalez et al., 2013, Wani et al., 2012, Wightwick et al., 2012). Although metalaxyl was used as a racemic mixture (ER=1), the enantioselective accumulation of metalaxyl has been reported in organisms and found to vary among the organisms (Wang et al., 2014, Xu et al., 2011, Zhang et al., 2012). However, the mechanisms for species-specific enantioselective biotransformation of metalaxyl have never been investigated. Although CYP450s consist of various subfamily enzymes, only some of them have been well studies relating to metabolism of xenobiotics such as CYP1A1, CYP1A2, CYP2B1, CYP2B2, CYP2E1, and CYP3A (Guengerich, 2001, Lu et al., 2013, Oropeza-Hernández et al., 2003; Vijaya Padma et al., 2014). In this study, therefore, the effects of metalaxyl on the six CYP450 enzymes were investigated in four vertebrate hepatic cell lines, including human hepatic HepG 2 cells, rat hepatic H4IIE cells, chicken hepatic LMH cells and grass carp hepatic L8824 cells. The residual concentrations and ER of metalaxyl were also determined in the medium of the four cells to reveal the enantioselective species-specific responses of CYP450s for metalaxyl.