title: Effect of cellular fatty acid alteration on adriamycin sensitivity in cultured L1210 murine leukemia cells.
abstract: We have investigated the effect of cellular fatty acid alteration on Adriamycin cytotoxicity using the L1210 lymphoblastic leukemia cell line. Cells growing in Roswell Park Memorial Institute Medium 1640 with 5% fetal bovine serum were modified with respect to fatty acid composition by supplementing their growth medium with 32 microM docosahexaenoic acid (22:6) or oleic acid (18:1). A soft agar clonogenic assay was then used to assess survival following incubation with Adriamycin. When exposed to the drug at a concentration of 0.4 microM, cells grown in the 22:6-supplemented medium were more sensitive (min of drug treatment required to reduce survival by 63% on the exponential portion of the survival curve, 64.9 +/- 4.2 min) to the cytotoxic effects of Adriamycin than cells grown in unsupplemented medium (min of drug treatment required to reduce survival by 63% on the exponential part of the survival curve, 106 +/- 9.7 min) (p less than 0.005). Cytotoxicity of L1210 cells grown in 18:1-supplemented medium was similar to that of cells grown in unsupplemented medium (min of drug treatment required to reduce survival by 63% on the exponential part of the survival curve, 126.6 +/- 9.1 min). The heightened sensitivity to Adriamycin of cells whose medium contained 22:6 increased as the concentration of fatty acid used to supplement the growth medium was increased. The cytotoxicity was also a function of the concentration of Adriamycin from 0.1 to 1.6 microM. When compared to cells grown in unsupplemented medium, those grown in 22:6-supplemented medium contained 3- to 4-fold more polyunsaturated fatty acids in their phospholipids, with a resultant doubling in the mean number of double bonds per fatty acid molecule. These data demonstrate that modification of cellular fatty acid composition may dramatically affect the sensitivity of a tumor cell to Adriamycin.
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004281:Docosahexaenoic Acids; D004317:Doxorubicin / Q000633:toxicity*; D005227:Fatty Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D007700:Kinetics; D007939:Leukemia L1210 / Q000503:physiopathology*; D050356:Lipid Metabolism; D051379:Mice; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D009829:Oleic Acids; D010743:Phospholipids; D004281:Docosahexaenoic Acids; D019301:Oleic Acid; D004317:Doxorubicin