Experimental chemical hepatocarcinogenesis: early membrane changes of significance for drug resistance.
Male Fischer F344 rats (180-220 g) were fed either a basal diet, a diet supplemented with 2-acetylaminofluorene (AAF) 0.02% (w/w) for up to 3 months or dietary tumor promoters. Normal or AAF-altered hepatic microsomes were compared with respect to drug-induced lipid peroxidation. A three-fold decrease was found in the ability of adriamycin to induce lipid peroxidation on AAF-altered and promoter-altered microsomes, compared to normal microsomes. A similar decrease was found when using a direct acting organic peroxidant. The microsomal hepatic lipid was extracted, and AAF-altered lipid was found to be a poorer substrate for adriamycin-mediated lipid peroxidation compared to normal microsomal lipid. Similar results were obtained with purified phosphatidylcholine from AAF-altered compared to normal microsomes. It was concluded that carcinogen treatment causes alterations in the microsomal phospholipids that render them less susceptible to lipid peroxidation, which is probably due to a carcinogen-induced decrease in the level of fatty acid saturation.
Carr
B I
BI
D015073:2-Acetylaminofluorene; D000818:Animals; D004032:Diet; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000648:ultrastructure*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000648:ultrastructure; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009249:NADP / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D008054:Lipid Peroxides; D009249:NADP; D004317:Doxorubicin; D015073:2-Acetylaminofluorene