Toxicity of nystatin and its methyl ester toward parental and hybrid mammalian cells

Abstract

Nystatin methyl ester (NME), the methyl ester derivative of the polyene macrolide antibiotic nystatin, is known to be effective against fungi and is now found to be relatively less toxic than the parent antibiotic nystatin (NYS) to animal cells in culture as measured by 51Cr release, cell survival at different posttreatment periods and cell growth. NYS and NME were tested on TK- mouse (B82) and hamster (B1) cells, HGPRT- mouse (RAG) cells, and on lysolecithin-fused cells selected in HAT medium and confirmed as B82-RAG and B1-RAG hybrids by chromosomal analysis plus polyacrylamide gel electrophoresis of lactate dehydrogenase. NME was less toxic and caused less immediate membrane damage than NYS when tested in all five cell systems. However, differences in innate polyene sensitivity were evident between the three parental cell types. B82 and B1 cells were more resistant than RAG cells to NYS and NME. B82-RAG hybrids reflected the higher level resistance of B82 parental cells, and B1-RAG hybrids reflected the higher level resistance of B1 cells. Where one parental cell type is relatively more polyene sensitive, the use of polyenes in the future may be applicable as selective agents in cell hybridization.