Biochem J. 1990 Jun 1;268(2):309-15.

Expression of human glutathione S-transferases in Saccharomyces cerevisiae confers resistance to the anticancer drugs adriamycin and chlorambucil.

Black SM, Beggs JD, Hayes JD, Bartoszek A, Muramatsu M, Sakai M, Wolf CR.

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Imperial Cancer Research Fund, University of Edinburgh Department of Biochemistry.

Abstract

Adaptation and resistance to chemicals in the environment is a critical part of the evolutionary process. As a result, a wide variety of defence systems that protect cells against chemical insult have evolved. Such chemical resistance mechanisms appear to play a central role in determining the sensitivity of human tumours to treatment with chemotherapeutic drugs. The glutathione S-transferases (GST) are important detoxification enzymes whose over-expression has been associated with drug-resistance. In order to evaluate this possibility we have expressed the human Alpha-class and Pi-class GST cDNAs that encode GST B1B1 and GST pi in the yeast Saccharomyces cerevisiae. The expression of GST B1B1 or GST pi resulted in a marked reduction in the cytotoxic effects of chlorambucil, a bifunctional alkylating agent, and an anthracycline, adriamycin. These data provide direct evidence that the over-expression of GST in cells can confer resistance to anticancer drugs.

PMID:: 2194447; [PubMed - indexed for MEDLINE]
PMCID: PMC1131433

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Expression of human glutathione S-transferases in Saccharomyces cerevisiae confers resistance to the anticancer drugs adriamycin and chlorambucil.

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