Isolation and characterization of Chinese hamster ovary cell mutants with altered sensitivity to high doses of tunicamycin.
A mutant, CTM422, resistant to low dose of tunicamycin (TM) was isolated from Chinese hamster ovary (CHO) cells, and it showed 7- to 10-fold higher resistance to TM than CHO. We further mutagenized CTM422, to isolate TM-high-resistant mutants which were resistant to about 100-fold higher dose of TM than CHO. The TM-high-resistant mutants (N101 and N102) acquired about 4-fold higher cross-resistance to 2-deoxy-d-glucose than CHO or CTM422, while both CHO and CTM422 showed similar sensitivity to 2-deoxy-d-glucose. TM-low-resistance appeared to be codominant, and TM-high-resistance was partially codominant against TM sensitivity, respectively. The transfer activity of N-acetylglucosamine from UDP-N-acetylglucosamine into the lipid fraction with CHO and CTM422 cell extracts was inhibited by TM to a similar extent, while the extract of N102 cells showed about 10-fold higher resistance to TM than CHO or CTM422.
D000818:Animals; D002460:Cell Line; D002469:Cell Separation; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D005260:Female; D005799:Genes, Dominant; D005944:Glucosamine / Q000031:analogs & derivatives*; D006822:Hybrid Cells / Q000187:drug effects; D009154:Mutation; D010053:Ovary; D014415:Tunicamycin / Q000494:pharmacology*
D014415:Tunicamycin; D005944:Glucosamine