Molecular docking analysis suggested that there are different orientations of interaction of 2,5,2',5'-TCB with the active sites (over the heme) of human and monkey CYP2A enzymes and that ligand interaction energies (U values) of bound protein-ligand complexes show structural relationships of interaction of TCBs and other ligands with active sites of CYP2A enzymes. None of these human and monkey CYP2A enzymes were catalytically active in oxidizing other TCB congeners, such as 2,4,3',4'-, 3,4,3',4'-, and 3,5,3',5'-TCB. Cynomolgus monkey CYP2A24, which shows 95% amino acid identity to human CYP2A6, catalyzed 4-hydroxylation of 2,5,2',5'-TCB at a higher rate (~0.3 min-1) than CYP2A26 (93% identity to CYP2A6, ~0.13 min-1) and CYP2A23 (94% identity to CYP2A13, ~0.008 min-1). Several human P450 enzymes, including CYP1A1, 1A2, 1B1, 2B6, 2D6, 2E1, 2C9, and 3A4, did not show any detectable activities in oxidizing 2,5,2',5'-TCB. Formation of 4-hydroxy-2,5,2',5'-TCB by CYP2A6 was greater than that of 3-hydroxy-2,5,2',5'-TCB and three other hydroxylated products. However, CYP2A6 oxidized 2,5,2',5'-TCB to form 4-hydroxylated products at a much higher rate (~1.0 min-1) than CYP2A13 (~0.02 min-1), based on analysis by LC-MS/MS. Дў,5,2',5'-Tetrachlorobiphenyl (TCB) induced Type I binding spectra with cytochrome P450 (P450 or CYP) 2A6 and 2A13, having Ks values of 9.4 and 0.51 ОјM, respectively.

2,5,2Вґ,5Вґ-Tetrachlorobiphenyl (#PCB52) (IARC Monograph, 2015 Mills et al., 2007) (Figure 1) is one of the PCB congeners identified in human milk and in foodstuffs at significant levels and has been extensively studied in its biological activities and metabolism. (2006determined the levels of PCB congeners in the human milk in Osaka and found that 12 major PCBs including three hepta-, two hexa-, four penta-, and four tetra-chlorobiphenyl congeners in milk decreased between 19, but the rate of elimination depends on the individual PCB congeners determined, probably due to their susceptibilities to be chemically degraded and enzymatically metabolized (Todaka et al., 2008 Arnich et al., 2009 Akutsu et al., 2005).

After cessation of production and use of commercial PCBs after 1970, the levels of PCBs in human tissues and milk have decreased yearly in Japan (Yakushiji et al., 1979 1984).However, due to their strong persistent nature, PCBs have been shown to be present at significant levels in environmental and biological samples (Kunita et al., 1984 Yakushiji et al., 1984). Sensitivity analysis indicated that the concentration of DL-PCBs and exposure frequency were the most effective parameters in increasing carcinogenic risk. In contrast, the lifetime cancer risk estimated for Bandar Anzali, Bandar Torkaman, and Rasht exceeded the threshold value of 1 Г— 10-6 suggested by United States Environmental Protection Agency. In all samples, non-carcinogenic risk of exposure to DL-PCBs was in safe level (Hazard Quotient < 1). The total maximum concentration was detected in Cyprinus carpio from Bandar Anzali, the minimum in Vimba vimba from Chalos. The average (standard deviation) of DL-PCBs in fish samples ranged from 232 (16) to 1156 (14) pg/g lipids. Probabilistic risk of exposure to DL-PCBs and sensitivity analysis were assessed using Monte Carlo simulation approach. Duncan's multi-scope test was used to compare the mean of DL-PCBs in different fish species and different cities. Five fish species (Oncorhynchus mykiss, Vimba vimba, Cyprinus carpio, Rutilus frisii kutum and Chelon saliens) were collected from 5 coastal cities of the Caspian Sea (25 samples per each city). In this study, the levels of 12 DL-PCBs congeners were measured in 125 fish samples of the Caspian Sea, Iran.

Among polychlorinated biphenyls (PCBs), dioxin-like PCBs (DL-PCBs) are of the most concern for human health.

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