Determinants of species susceptibility to oxidative stress: A comparison of channel catfish and brown bullhead

Xenobiotic-mediated productions of reactive oxygen species, via enzymemediated redox cycling, have been implicated in a variety of toxicological 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 (Ameriurus nebulosus)-in terms of basic biochemical characteristics related to oxidative stress. This has included analysis of microsomal redox cycling of model xenobiotics (e.g. menadione) as well as antioxidant and other detoxifying enzymes in hepatic tissue of the two species. In addition, endpoints of oxidative stress, such as altered glutathione status and oxidative DNA damage, were examined. These studies have revealed numerous qualitative and quantitative differences between the two species both in terms of basal enzyme activities and in species response to model prooxidants. For example, bullhead appear to possess a greater capacity for microsomal redox cycling of xenobiotics, but have glutathione-dependent defense systems less able to withstand oxidative challenge. These and other interspecific differences have allowed for an improved understanding of the basic mechanisms which may underly species susceptibility to oxidative stress and critical manifestations such as cancer.