| Summary: | Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution September 2003 Contamnant exposure has been associated with toxic effects in marine mammals. Studies on early biochemical and molecular responses prior to, but associated with, contaminant-induced toxicity will aid in understanding the susceptibility of cetaceans to such exposures. Cytochrome P450 1A1 (CYP1A1) induction by planar halogenated aromatic hydrocarbons, including certain polychlorinated biphenyls (PCBs), has been correlated with toxic effects in rodents. CYP1A1 expression was measured in multiple organs from beluga whales and white-sided dolphins and integument biopsies from bottlenose dolphins. Age and sex do not appear to influence CYP1A1 expression in these species. Mono-artha PCB concentrations were correlated with CYP1A1 in bottlenose dolphin integument and white-sided dolphin liver. White-sided dolphins, with PCBs concentrations six times higher than Arctic beluga, have lower hepatic CYP1A1 expression. Beluga whales thus appear very sensitive to the induction of CYP1A1 by PHAHs. These studies demonstrate that comparative studies between cetacean species, with reference to experimental work in model organisms, could determine the relative susceptibility of cetaceans to contaminant exposures. Aromatase is the enzyme responsible for estrogen production and recent studies suggest that PCBs may alter its activity or expression. We determined the sequence and characterized the catalytic properties of a cetacean aromatase, which was similar to other mammalian aromatases. Evolutionary analyses of vertebrate aromatases revealed striking functional conservation. Although much work is required, these data show that similar to CYP1A1, aromatase studies in other mammals are applicable to cetacean species. Experimental work in model organisms, coupled with careful studies with cetacean tissues, could infer the physiological role ...
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