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  • Title: Experimental chemical hepatocarcinogenesis: early membrane changes of significance for drug resistance.
    Author: Carr BI.
    Journal: J Cell Physiol Suppl; 1986; 4():59-63. PubMed ID: 3462192.
    Abstract:
    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.
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