Peroxisome proliferators constitute an important group of xenobiotics with therapeutic, societal, and agricultural importance. Because these agents induce liver tumors in rodents, but fail to exert the genotoxic or mutagenic effects directly in short-term in vitro test systems, they are considered a paradigm to investigate the mechanisms of nongenotoxic hepatocarcinogenesis. A concerted cell biological, biochemical, and molecular biological approach is essential to understand the relationship of xenobiotic-induced peroxisome proliferation to the eventual development of liver tumors. It is our intent to provide insight into the mechanisms responsible for tissue specificity and species differences in the biological responses to peroxisome proliferators.
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