It would be worth studying b catenin dependent transcrip tion in relation to carcinogenicity. Gefitinib DEHP effects in the SHE model compared to rats and mice While the expression of cyp1b1 and cyp2e1 was up regulated and cyp2f2 under expressed, no change in expression level of CYP4 genes was found using DD and qPCR after DEHP exposure in our experimental condi tions. CYP4 genes are said to be involved in peroxisome proliferation. Eveillard et al. who studied the involvement of DEHP in lipidogenesis in rats, found a slight increase in the PPARa level after 21 days of oral exposure to DEHP. They registered a significant increase in CYP4 levels after 14 days and after 21 days of exposure. On the other hand, we found no increased mRNA level of CYP4 and PPAR genes in DEHP treated SHE cells.

This underlines that the genes expression changes noted in the present study are independent of PPARs induction. Eveillard et al. found that induced expression of cyp2b10 by DEHP was also independent of PPARa induction but CAR depen dent. No change in CAR expression was registered in SHE cells, which may explain why no change in cyp2b10 was noted. Our results are consistent with the study of Ren et al. who identified DEHP regulated genes independent of PPARa and CAR in rats and mice. In our study, lipogenesis and xenobiotic metabolism pathways were impacted by DEHP, but not in a major prior way. This may be explained by the lower sensitivity of the hamster model compared with rats and mice to peroxisome proliferators. Indeed, the Syrian hamster model presents an intermediate response between rats or mice and humans who are known to be non responsive to PP induction.

The hamster model, like humans, is less responsive to PP induction than rats and mice, which is an advantage for mechanistic studies of PP effects and for screening human chemical carcinogens. On the other hand, three genes and 5 gene isoforms were commonly found in our study and those carried out by Eveillard et al. suggesting a pattern of response specific to DEHP. Takashima et al. also found similar responses in DEHP treated mice. Up regulation of rab1b, a RAS oncogene family member involved in cellular signal transduction or survival, was found in the latter study and in the present one. b Tubulin was clearly over expressed in mice, a trend which was noted in our study.

Some gene isoforms of cadherin, nidogen, cyp1 family genes or LIM domain were also impacted in the liver of mice exposed to DEHP. DEHP effects on transcription factors Other genes identified by Differential Display and involved in transcription and signal transduction path ways Carfilzomib or apoptosis were also targeted by DEHP. A signif icant under expression of p53 was found after 24 hrs of DEHP exposure using Differential Display and qPCR. This under expression is in line with the anti apoptotic effects of DEHP.