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.
Original language | English (US) |
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Pages (from-to) | 309-315 |
Number of pages | 7 |
Journal | Biochemical Journal |
Volume | 268 |
Issue number | 2 |
DOIs | |
State | Published - 1990 |
Externally published | Yes |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology