Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Expression of human glutathione S-transferases in Saccharomyces cerevisiae confers resistance to the anticancer drugs adriamycin and chlorambucil
AU - Black, S M
AU - Beggs, J D
AU - Hayes, J D
AU - Bartoszek, A
AU - Muramatsu, M
AU - Sakai, M
AU - Wolf, C R
PY - 1990/6/1
Y1 - 1990/6/1
N2 - 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.
AB - 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.
KW - Alkylating Agents/pharmacology
KW - Chlorambucil/pharmacology
KW - DNA, Fungal/biosynthesis
KW - DNA, Recombinant/biosynthesis
KW - Doxorubicin/pharmacology
KW - Drug Resistance, Microbial
KW - Escherichia coli/genetics
KW - Gene Expression
KW - Glutathione Transferase/biosynthesis
KW - Microbial Sensitivity Tests
KW - Saccharomyces cerevisiae/drug effects
U2 - 10.1042/bj2680309
DO - 10.1042/bj2680309
M3 - Journal article
VL - 268
SP - 309
EP - 315
JO - Biochemical Journal
JF - Biochemical Journal
SN - 0264-6021
IS - 2
ER -