Chlorotrifluoroethylene trimer and tetramer are inducers of the CYP4A subfamily.
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 peroxisomal beta-oxidation of fatty acids as assessed by increases in palmitoyl-coenzyme A (CoA) oxidation, thus confirming these oligomers as peroxisome proliferators. Consistent with these conclusions, both trimer and tetramer increased the hydroxylation of lauric acid indicating that the CTFEs were inducers of the CYP4A subfamily, a conclusion further supported by substantial increases in the steady-state levels of the cognate CYP4A1 mRNA as determined by northern blotting. The liver appeared to be more susceptible to induction than the kidney and the CTFE tetramer was more potent than the trimer. These results are discussed with respect to both the differential hepatotoxicity, and biotransformation/disposition of the two polyhalogenated oligomers.
Diaz
M J
MJ
School of Biological Sciences, University of Surrey, Guildford, U.K.
Chinje
E
E
Kentish
P
P
Jarnot
B
B
George
M
M
Gibson
G G
GG
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002332:Carnitine O-Acetyltransferase; D017402:Chlorofluorocarbons / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D011108:Polymers; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
D017402:Chlorofluorocarbons; D011108:Polymers; D012333:RNA, Messenger; D010171:Palmitoyl Coenzyme A; D003577:Cytochrome P-450 Enzyme System; C016304:chlorotrifluoroethylene; D006899:Mixed Function Oxygenases; D002332:Carnitine O-Acetyltransferase