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

Black, SM, Beggs, JD, Hayes, JD et al. (1990). Expression of human glutathione S-transferases in Saccharomyces cerevisiae confers resistance to the anticancer drug adriamycin and chlorambucil . 268(2), 309-315. 10.1042/bj2680309

cited authors

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

fiu authors

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 π in the yeast Saccharomyces cerevisiae. The expression of GST B1B1 or GST π 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.

publication date

  • January 1, 1990

Digital Object Identifier (DOI)

start page

  • 309

end page

  • 315

volume

  • 268

issue

  • 2