Hepatocarcinogenesis cause

HayashiF, Tamura H, Yamada J, et al. 1994. Characteristics of the hepatocarcinogenesis cause by dehydroepiandrosterone, a peroxisomeproliferator, in maleF-344 rats. Carcinogenesis 15(10) 2215-2219. 

Trapp, C., Schwarz, M., and Epe, B. (2007). The peroxisome proliferator WY-14,643 promotes hepatocarcinogenesis caused by endogenously generated oxidative DNAbase modifications in repair-deficient Csbm/m/Oggl-/- mice. Cancer Res 67, 5156-5161. 

Persistent activation of PPARa can induce the development of hepatocellular carcinoma in susceptible rodent species by a nongenotoxic mechanism, i.e., one that does not involve direct DNA damage by peroxisome proliferator chemicals or their metabolites. This hepatocarcinogenic response is abolished in mice deficient in PPARa, underscoring the central role of PPARa, as opposed to that of two other mammalian PPAR forms (PPARy and PPAR5), in peroxisome proliferator chemical-induced hepatocarcinogenesis. Other toxic responses, such as kidney and testicular toxicities caused by exposure to certain phthalate... 

Research has shown clearly that PPARa is necessary for hepatocarcinogenesis in mice. Thus, the PPARa-agonist drug Wy-14643 causes a 100% incidence of liver tumors in wild-type mice, yet PPARa-null mice are resistant. This has been confirmed using the drug bezafibrate. 

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