DETERMINANTS OF SPECIES SUSCEPTIBILITY TO OXIDATIVE STRESS - A COMPARISON OF CHANNEL CATFISH AND BROWN BULLHEAD

Xenobiotic-mediated productions of reactive oxygen species, via enzyme -mediated redox cycling, have been implicated in a variety of toxicolo gical phenomena including lipid-peroxidation, enzyme inactivation and oxidative DNA damage leading to cancer. A comparison was undertaken of two benthic freshwater fish species that appear to differ markedly in their susceptibility to chemical carcinogenesis-the channel catfish ( Ictalurus punctatus) and the more cancer-prone brown bullhead (Ameriur us nebulosus)-in terms of basic biochemical characteristics related to oxidative stress. This has included analysis of microsomal redox cycl ing of model xenobiotics (e.g. menadione) as well as antioxidant and o ther detoxifying enzymes in hepatic tissue of the two species. In addi tion, endpoints of oxidative stress, such as altered glutathione statu s and oxidative DNA damage, were examined. These studies have revealed numerous qualitative and quantitative differences between the two spe cies both in terms of basal enzyme activities and in species response to model prooxidants. I;or example, bullhead appear to possess a great er capacity for microsomal redox cycling of xenobiotics, but have glut athione-dependent defense systems less able to withstand oxidative cha llenge. These and other interspecific differences have allowed for an improved understanding of the basic mechanisms which may underly speci es susceptibility to oxidative stress and critical manifestations such as cancer.