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

Black, S M and Beggs, J D and Hayes, J D and Bartoszek, A and Muramatsu, M and Sakai, M and Wolf, C R (1990) Expression of human glutathione S-transferases in Saccharomyces cerevisiae confers resistance to the anticancer drugs adriamycin and chlorambucil. Biochemical Journal, 268 (2). pp. 309-315. ISSN 0264-6021

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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.

Item Type:
Journal Article
Journal or Publication Title:
Biochemical Journal
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/1300/1312
Subjects:
ID Code:
132586
Deposited By:
Deposited On:
09 Apr 2019 13:40
Refereed?:
Yes
Published?:
Published
Last Modified:
23 Jun 2020 12:08