Proceedings in uncovering the mechanism behind peroxisome proliferator-induced hepatocarcinogenesis.
The cancer risk assessment of peroxisome proliferators (PPs) has been a matter of debate for decades. PPs are non-genotoxic carcinogens that cause liver tumours in rodents. There is considerable evidence that humans are refractory to the carcinogenic effect of PPs. Still, some toxicologists argue that these chemicals should be considered carcinogenic until the opposite has been proven. To solve this matter, much work has been dedicated to uncovering the mode of action of PPs. The proceedings are reviewed and it is discussed whether these provide an explanation for the observed interspecies differences and shed a new light on human health risk assessment. The efforts in the past years have significantly increased our understanding of the pathways involved, but have also raised new questions. The question why humans seem to be refractory is yet to be answered. From this point of view, the safety assessment of PPs to humans therefore remains an issue of discussion.
Bosgra
Sieto
S
Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80.176, NL-3508 TD Utrecht, The Netherlands.
Mennes
Wim
W
Seinen
Willem
W
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D047493:PPAR alpha / Q000378:metabolism; D020025:Peroxisome Proliferators / Q000506:poisoning* / Q000633:toxicity*; D020675:Peroxisomes / Q000378:metabolism*; D051381:Rats
D002273:Carcinogens; D005227:Fatty Acids; D047493:PPAR alpha; D020025:Peroxisome Proliferators