Phosphorylation of 13 kDa nuclear protein in hepatocarcinomas induced by peroxisome proliferators

Peroxisome proliferators (PPs) are nongenotoxic compounds causing the emergence of hepatocellular carcinoma in rodents, but the mechanisms of the hepatocarcinogenesis have been unclear. The authors examined the changes in phosphorylation of nuclear proteins after treatment with (4-chloro-6-[2,3-xylidino]-2-pyrimidinylthio) acetic acid (Wy-14,643). Wy-14,643 (0.1% w/w in diet) was given orally to male F-344 rats for up to 80 wk. In the hepatocarcinomas induced by Wy-14,643, phosphorylation of 13 kDa nuclear protein (NP 13), which was resistant to alkaline treatment, was significantly increased. NP 13 phosphorylation gradually increased, dependent on treatment period. Furthermore, in the hepatocarcinomas induced by other PP, di(2-ethylhexyl)phthalate, increase in NP13-phosphorylation was also observed. Therefore, NP 13-phosphorylation may relate to development of preneoplastic or neoplastic lesions induced by PPs.