Specific profile of liver microsomal cytochrome P-450 in Dolphin and Whales

Abstract

The cytochrome P-450-linked monooxygenase system in liver microsomes from three species of cetaceans including short-finned pilot whale ( Globicephala macrorhynchus), striped dolphin ( Stenella coeruleoalba) and killer whale ( Orcinus orca) were investigated with reference to the catalysis of the model substrates aldrin, aniline, benzo[a]pyrene, 7-ethoxyresorufin, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), and 2-amino-3,5-dimethylimidazo[4,5-f]-quinoxaline (MeIQ). Cytochrome P-450 contents in cetacean liver microsomes ranged from 0·17 to 0·21 nmol per mg protein. In short-finned pilot whale fetal liver microsomes contained only about 0·04 nmol per mg protein; monooxygenase activities were also lower than those measured in immature or mature individuals. No sex-related differences and developmental changes in cytochrome P-450-linked monooxygenase activities were observed in this species. Interestingly, the cetaceans showed relatively low aldrin epoxidase (ALDE) and aniline hydroxylase (AH) activities, whereas benzo[a]pyrene hydroxylase (AHH) and 7-ethoxyresorufin O-deethylase (EROD) activities were observed to be comparable to the activities of liver microsomes from untreated male Sprague-Dawley rats. Polyclonal antibodies raised against a 3-methylcholanthrene (MC) inducible form of rat cytochrome P-450 (P-450c) inhibited AHH and EROD activities and the metabolic activation of MeIQ by liver microsomes from short-finned pilot whales. These results suggest that the cytochrome P-450 isozyme(s) which is (are) orthologous to rat cytochrome P-450c have an important role in some of the drug oxidation reactions in cetacean liver microsomes.