Secondary mutation resistant to 7-ketocholesterol rescues a sterol metabolic defect in amphotericin B-resistant Chinese hamster cell line.
Amphotericin B-resistant mutants isolated from Chinese hamster V79 cells (1) are defective in cholesterol synthesis and more sensitive to an oxygenated sterol analog, 7-ketocholesterol, than their parental cell line. We isolated 7-ketocholesterol-resistant mutants from an amphotericin B-resistant mutant, AMBR-1. The 7-ketocholesterol-resistant mutants had regained increased level of free cholesterol, and they showed somewhat similar dose-response curves to amphotericin B as that of V79. Sterol synthesis from acetate, but not from mevalonate, in 7-ketocholesterol-resistant clones was threefold higher than that of AMBR-1. 7-Ketocholesterol-resistant clone, unlike AMBR-1, could form colonies in the presence of lipoprotein-depleted serum. The results are discussed in terms of probable change in the sterol biosynthetic pathway by the different lesions.
D000666:Amphotericin B / Q000633:toxicity*; D000818:Animals; D002449:Cell Aggregation; D002460:Cell Line; D002470:Cell Survival; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000096:biosynthesis*; D002999:Clone Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005838:Genotype; D007653:Ketocholesterols / Q000633:toxicity*; D009154:Mutation
D007653:Ketocholesterols; D000666:Amphotericin B; D002784:Cholesterol