Rodent Responses To Peroxisome Proliferators — A Receptor-Mediated Phenomenon?

摘要: The phenomenon of rodent peroxisome proliferation was first observed some years ago when the hypolipidaemic drug clofibrate administered to rats. Since then, a wide variety structurally diverse and industrially important compounds have been shown similar effects; these include other drugs, leukotriene antagonists, herbicides plasticisers (for review, see Reddy & Lalwani, 1982). In addition increases in size number hepatic peroxisomes, proliferators (PPs) susceptible species also bring about induction peroxisomal enzymes, cause Sphase ultimately carcinogenesis liver (Reddy et al, 1980), although potency differs considerably terms their carcinogenicity. This hepatocarcinogenesis is context human risk assessment, since humans are exposed many PPs both environmentally otherwise. termed non-genotoxic carcinogens they almost exclusively negative routine genotoxicity assays. raises question as mechanism carcinogenicity compounds. It has proposed that generation hydrogen peroxide through increase fatty acid poxidation causes DNA damage indirectly oxidative stress. Perhaps more likely, however suggestion PPs, by inducing replication, able ‘fix’ spontaneous environmentally-induced mutations which eventually give rise tumours (Cattley 1989).