Imidazole-resistant phenotype and virus transformation in cultured rat cells.
Compared to an untransformed rat cell line, 3Y1, adenovirus 12-transformed cell lines of 3Y1 were highly sensitive to the cytotoxic action of an imidazole antibiotic, clotrimazole. In contrast, SV40-transformed rat cell lines derived from the 3Y1 cell line showed no appreciable difference in the response to clotrimazole when compared to 3Y1 cells. Clotrimazole-resistant clones, WCT-1 and WCT-2, which were spontaneously isolated from the adenovirus 12-transformed cell line W5, showed 5- to 10-fold higher resistance than did W5; the dose-response curves of clotrimazole-resistant clones were similar to those of the untransformed 3Y1 cells. The growth of 3Y1 cells was blocked in the presence of 1% serum, whereas those of W5, WCT-1, and WCT-2 cells were only slightly affected by the same dose of serum in the medium. The membrane fractions of 3Y1, W5, and WCT-1 cells were found to contain similar cholesterol:phospholipid ratios. The phospholipid composition in the membrane fraction of line WCT-1 was similar to that of line W5 but not to that of line 3Y1. By contrast, the fatty acid composition was specifically altered in clotrimazole-resistant clones; cellular contents and some species of fatty acid such as 16:1, 18:2, and 20:4 in WCT-1 and WCT-2 cells were similar to those of 3Y1 but not to those of W5 cells. Differential sensitivities of various cell lines to clotrimazole are discussed in relation to the lipid composition.
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D002462:Cell Membrane / Q000032:analysis; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002849:Chromatography, Gas; D003022:Clotrimazole / Q000633:toxicity*; D004351:Drug Resistance; D005227:Fatty Acids / Q000032:analysis; D007093:Imidazoles / Q000633:toxicity*; D007700:Kinetics; D008563:Membrane Lipids / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D010743:Phospholipids / Q000032:analysis; D051381:Rats
D005227:Fatty Acids; D007093:Imidazoles; D008563:Membrane Lipids; D010743:Phospholipids; D003022:Clotrimazole