title: Cellular resistance to bleomycin in Saccharomyces cerevisiae is not affected by changes in bleomycin hydrolase levels.
abstract: Bleomycin is a glycopeptide drug that exerts potent genotoxic potential and is highly effective in the treatment of certain cancers when used in combination therapy. Unfortunately, however, tumors often develop resistance against bleomycin, and the mechanism of this resistance remains unclear. It has been postulated that bleomycin hydrolase, a protease encoded by the BLH1 gene in humans, may account for tumor resistance to bleomycin. In support of such a notion, earlier studies showed that exogenous expression of yeast Blh1 in human cells can enhance resistance to bleomycin. Here we show that (i) yeast blh1delta mutants are not sensitive to bleomycin, (ii) bleomycin-hypersensitive yeast mutants were no more sensitive to this agent upon deletion of the BLH1/LAP3/GAL6 gene, and (iii) overproduction of Blhl in either the parent or bleomycin-hypersensitive mutants did not confer additional resistance to these strains. Therefore, yeast Blh1 apparently has no direct role in protecting this organism from the lethal effects of bleomycin, even though the enzyme can degrade the drug in vitro. Clearly, additional studies are required to establish the actual biological role of Blh1 in yeast.
authors.affiliation: Maisonneuve-Rosemont Hospital, Guy-Bernier Research Center, 5415, boul. de l'Assomption, Montreal, QC H1T 2M4, Canada.
authors.forename: Hujie
authors.initials: H
authors.lastname: Wang
authors.forename: Dindial
authors.initials: D
authors.lastname: Ramotar
mesh_terms: D001761:Bleomycin / Q000494:pharmacology*; D015153:Blotting, Western; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D025141:Drug Resistance, Fungal; D015966:Gene Expression Regulation, Fungal; D007120:Immunochemistry; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics
chemical_list: C096739:IMP2 protein, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D001761:Bleomycin; D003546:Cysteine Endopeptidases; C031262:bleomycin hydrolase