CHLOROTRIFLUOROETHYLENE TRIMER AND TETRAMER ARE INDUCERS OF THE CYP4ASUBFAMILY

Male Wistar albino rats were treated for a 7 day period with equimolar doses of the trimer and tetramer oligomers of chlorotrifluoroethylene (CTFE), resulting in significant hepatomegaly for both compounds. In addition, both trimer and tetramer significantly induced the peroxisom al beta-oxidation of fatty acids as assessed by increases in palmitoyl -coenzyme A (CoA) oxidation, thus confirming these oligomers as peroxi some proliferators. Consistent with these conclusions, both trimer and tetramer increased the hydroxylation of lauric acid indicating that t he CTFEs were inducers of the CYP4A subfamily, a conclusion further su pported by substantial increases in the steady-state levels of the cog nate CYP4A1 mRNA as determined by northern blotting. The liver appeare d to be more susceptible to induction than the kidney and the CTFE tet ramer was more potent than the trimer. These results are discussed wit h respect to both the differential hepatotoxicity, and biotransformati on/disposition of the two polyhalogenated oligomers.