Glutathione-related factors are not correlated with sensitivity of human tumour cells to actinomycin D.
Glutathione (GSH) contents and activities of glutathione S-transferases (GST), glutathione reductase (GSH-RD), glutathione peroxidase (GSHpx) and glutathione conjugate export pump (GS-X pump) were determined in eight human tumour cell lines with different sensitivities to melphalan, a substrate of glutathione conjugation, and actinomycin D which has not been shown to be detoxified by glutathione-related mechanisms. Chang liver cells with highest GSH content and highest activities of GST, GSH-RD, GSHpx and GS-X pump were found to be most resistant to melphalan. Statistical analysis showed significant correlations between sensitivities of the human tumour cells to melphalan and the glutathione-related factors (r = 0.72-0.79; except for GST, r = 0.65, P = 0.08), while there were no significant correlations observed between sensitivities of the human tumour cells to actinomycin D and all the glutathione-related factors tested (r = -0.25-0.14). Significant correlations of the glutathione-related factors to resistance of human tumour cells to melphalan, a substrate of glutathione conjugation, but not to resistance of the human tumour cells to actinomycin D which has not been shown to be detoxified by glutathione-related mechanisms suggested that glutathione-related mechanisms contribute to drug resistance by increased detoxification of the drugs involved.
Zhang
K
K
Department of Experimental Surgery, Singapore General Hospital, Singapore. geskai@sgh.gov.sg
Yang
E B
EB
Zhao
Y N
YN
Wong
K P
KP
Mack
P
P
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology / Q000627:therapeutic use; D003609:Dactinomycin / Q000494:pharmacology* / Q000627:therapeutic use; D004352:Drug Resistance, Microbial; D019008:Drug Resistance, Neoplasm; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D008558:Melphalan / Q000494:pharmacology / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D003609:Dactinomycin; D005978:Glutathione; D008558:Melphalan