Hepatic nuclear envelope cytochrome P-450 in rats fed 2-acetylaminofluorene. Effect of dietary fats and butylated hydroxytoluene.
Early losses of nuclear envelope (NE) cytochrome P-450 occur during 2-acetylaminofluorene (AAF)-hepatocarcinogenesis. Butylated hydroxytoluene (BHT), which protects against AAF in rats fed high fat diets, preserves NE P-450 suggesting that the latter may be required for AAF detoxification. AAF-hepatocarcinogenesis is enhanced by increasing the amount or degree of unsaturation of dietary fats. The present studies show that in rats fed AAF in high fat diets BHT preservation of NE P-450 is considerably shorter (3 weeks) with polyunsaturated than with saturated fat (9 weeks). In rats fed AAF in a low fat diet, where BHT does not modify the low tumor incidence, there is a bimodal effect on NE P-450. In controls and AAF-fed rats, BHT causes significant induction of NE P-450 at 1-3 weeks. At 9-16 weeks BHT has no effect on controls and only partially preserves NE P-450 in AAF-fed rats. Due to time constraints, livers could not be utilized fresh, but they were kept frozen at -80 degrees C until processed. Thus, specimens from all groups underwent identical treatment for purposes of comparative studies.
Carubelli
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Molecular Toxicology Research Group, Oklahoma Medical Research Foundation, Oklahoma City 73104.
McCay
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D015073:2-Acetylaminofluorene / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002467:Cell Nucleus / Q000201:enzymology*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis*; D004041:Dietary Fats / Q000008:administration & dosage*; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains
D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D002084:Butylated Hydroxytoluene; D003577:Cytochrome P-450 Enzyme System; D015073:2-Acetylaminofluorene