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Polychlorinated biphenyls (PCBs) have been demonstrated to modulate marine mammal immune functions; however, the underlying mechanisms involved are poorly understood. Cytosolic calcium (Ca2+) is an important second messenger involved in numerous leukocyte functions. The direct effects of in vitro exposure to PCBs on Ca2+ mobilization were evaluated in leukocytes isolated from bottlenose dolphins, beluga whales, and B6C3F1 mice. Concentration- and time-response experiments with three non-coplanar PCBs (138, 153, 180), one coplanar PCB (169), and TCDD were tested. Exposure to the three non-coplanar PCBs significantly increased cytosolic Ca2+ in dolphin neutrophils, while PCB 180 significantly increased cytosolic Ca2+ in beluga neutrophils. Two non-coplanar PCBs (138 and 153) significantly increased Ca2+ in beluga monocytes, yet the response was delayed compared to that in neutrophils. Neither PCBs nor TCDD increased cytosolic Ca2+ in mouse neutrophils or monocytes. In experiments with Ca2+-free medium, only PCB 153 increased cytosolic Ca2+ in dolphin neutrophils, though the increase was less than that observed with Ca2+-supplemented medium, suggesting that extracellular Ca2+ was the predominant source for the rise in cytosolic Ca2+. Furthermore, in cells incubated with Ca2+-free medium, a significant increase in cytosolic Ca2+ was induced by thapsigargin following PCB exposure, indicating that intracellular Ca2+ was available, yet not mobilized by the PCBs, and further suggesting that PCBs mobilize extracellular Ca2+. These results demonstrate for the first time the direct effects of non-coplanar PCBs on Ca2+ mobilization in marine mammals, which may be involved in the modulation of phagocytosis previously observed in these species.

Contaminants described as organochlorines (OCs; e.g., polychlorinated biphenyls [PCBs]) are present in tissues of marine mammals, including beluga whales (Delphinapterus leucas), but the complexity of contaminant exposure often is not fully known. The PCBs, OC pesticides, polybrominated diphenyl ether (PBDE) flame retardants, methylsulfonyl (MeSO2)- and hydroxy (OH)-PCB metabolites, and OH-PBDEs and methoxylated (MeO)-PBDEs were determined in the liver of beluga whales from two Canadian populations: the St. Lawrence Estuary (SLB; n=6), and western Hudson Bay in the Canadian Arctic (CAB; n=11). The sigmaPCB, sigmaDDT, and sigmaPBDE concentrations were higher (p < 0.05) in SLB versus CAB. Of 18 detectable OH-PCBs in SLB (mainly 4-OH-CB107, 4-OH-CB112, and 4'-OH-CB120), only 4'-OH-CB120 was found in CAB. The sigmaOH-PCB concentrations were less than 0.2% of the sigmaPCBs in both populations but were higher (p < 0.05) in SLB (65 +/- 22 ng/g lipid wt) than in CAB (3.1 +/- 0.5 ng/g lipid wt). The sigmaMeSO2-PCB concentrations were higher in SLB (3801 +/- 1322 ng/g lipid wt) relative to CAB (77 +/- 23 ng/g lipid wt) and were 11 and 4%, respectively, of the sigmaPCB concentrations. Of the 15 OH-PBDEs, only two congeners were detectable, but not quantifiable (notably 2'-OH-BDE 68 and 6-OH-BDE 47), in animals from both populations. Of the 15 MeO-PBDEs, 4'-MeO-BDE 17 and 6-MeO-BDE 47 in the SLB (n=2) and 2'-MeO-BDE 68 and 6-MeO-BDE 47 in the CAB (n=2) had concentrations from 20 to 100 ng/g lipid weight. The OH-PBDEs and MeO-PBDEs most likely are of natural origin and accumulated in beluga whales, whereas the OH-PCBs and MeSO2-PCBs are metabolites derived from accumulated PCBs. Canadian beluga whale liver contains previously unidentified organohalogen contaminants and metabolites and, thus, a complexity of contaminant exposure that may be impacting the health of Canadian beluga whale populations.

Although polychlorinated biphenyls (PCBs) and polybrominated diphenyl ether (PBDE) flame retardants are important organic contaminants in the tissues of marine mammals, including those species from the Arctic, there is exceedingly little direct evidence on congener-specific biotransformation. We determined and compared the in vitro metabolism of environmentally relevant PCB (4,4'-di-CB15, 2,3',5-tri-CB26, 2,4,5-tri-CB31, 2,2',5,5'-tetra-CB52, 3,3',4,4'-tetra-CB77, 2,2',4,5,5'-penta-CB101, 2,3,3',4,4'-penta-CB105 and 2,3',4,4',5-penta-CB118), and PBDE (4,4'-di-BDE15, 2,4,4'-tri-BDE28, 2,2',4,4'-tetra-BDE47, 2,2',4,5'-tetra-BDE49, 2,2',4,4',5-penta-BDE99, 2,2',4,4',6-penta-BDE100, 2,2',4,4',5,5'-hexa-BDE153, 2,2',4,4',5,6'-hexa-BDE154 and 2,2',3,4,4',5',6-hepta-BDE183) congeners using hepatic microsomes of a beluga whale (Delphinapterus leucas) from the Arviat (western Hudson Bay) area of the Canadian Arctic. Ortho-meta bromine-unsubstituted BDE15, BDE28 and BDE47 were significantly metabolized (100%, 11% and 5% depleted, respectively) by beluga, whereas control rat microsomes (from pooled male Wistar Han rats) metabolized BDE28, BDE49, BDE99 and BDE154 (13%, 44%, 11% and 17% depleted, respectively). CB15 and CB77 (putative CYP1A substrates) were more rapidly metabolized (100% and 93% depleted, respectively) by male beluga than CB26 and CB31 (CYP1A/CYP2B-like) (25% and 29% depleted, respectively), which were more rapidly metabolized than CB52 (CYP2B-like) (13% depleted). Higher chlorinated CB101 and CB105 showed no depletion. Rat control microsomes metabolized CB15 to a lesser extent (32% depleted) than beluga, but much more rapidly transformed CB52 (51% depleted, respectively). Within the 90 min in vitro assay time frame, the preference was towards metabolism of ortho-meta unsubstituted congeners (for both PCBs and PBDEs) in beluga whale, whereas for rat controls, meta-para unsubstituted congeners also substantially metabolized. For both beluga whale and rat, metabolic rates were inversely associated with the degree of halogenation. For the rapidly biotransformed CB15 and BDE15, water-soluble OH-metabolites were detected after incubation. These results indicate that CYP-mediated oxidative hepatic biotransformation is a metabolic pathway in the toxicokinetics of both PCB and PBDE congeners in beluga whales and in the rat model. This may suggest that the formation of potentially toxic oxidative PCB and PBDE products (metabolites), in addition to the parent pollutants, may be contributing to contaminant-related stress effects on the health of beluga whale.