Peroxisome proliferators: Paradigms and prospects

摘要: Abstract Peroxisome proliferators are a structurally diverse group of chemicals. They include fibrate hypolipidaemic drugs, phthalate ester plasticisers, phenoxy acid herbicides, azole antifungal and perfluorinated fatty acids. This presentation will focus on the common pleotropic responses produced by these compounds including hepatomegaly (hyperplasia hypertrophy), activation cell cycle S-phase ploidy changes, cytochrome P4504A1 induction, morphometric/biochemical analysis peroxisome proliferation stimulation growth factors, oncogene activation. Consideration also be given to role recently described Proliferator Activated Receptor in hepatic responses. uniformly negative wide range genotoxicity tests, but nevertheless complete carcinogens, particularly rodent liver. Mechanisms nonmutagenic carcinogenesis discussed active oxygen hypothesis involving 8-hydroxydeoxyguanosine adducts possibility promoting preexisting lesions clonal expansion, eventually resulting frank tumorigenesis. Finally, consideration risk assessment humans discussed.