Variation of choline-substituted lipid metabolism in doxorubicin-resistant leukemia cells.
In adriamycin-resistant murine (FLC) and human (K562) leukemia cells, phosphatidylcholine increases and phosphatidylethanolamine decreases compared to adriamycin-sensitive lines. This change is due to an increase in phosphatidylethanolamine methylation. The choline pathway of phosphatidylcholine biosynthesis is also disturbed in resistant cells with a blocking step of CDP-phosphocholine transferase and a decrease in sphingomyelinase activity. These changes in phospholipid metabolism are suggested to be responsible for the changes in membrane fluidity reported previously (Tapiero et al, 1986) for resistant cells.
Dubois
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Laboratoire de Pharmacologie Moléculaire et Cellulaire, Hôpital Paul Brousse, Villejuif, France.
Tapiero
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H
D000818:Animals; D004317:Doxorubicin / Q000494:pharmacology*; D004352:Drug Resistance, Microbial; D006801:Humans; D066298:In Vitro Techniques; D007938:Leukemia / Q000473:pathology*; D007942:Leukemia, Experimental / Q000473:pathology; D051379:Mice; D010713:Phosphatidylcholines / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D004317:Doxorubicin; D013108:Sphingomyelin Phosphodiesterase