GLUTATHIONE, GLUTATHIONE-S-TRANSFERASE AND P-170 GLYCOPROTEIN IN METASTASES OF MALIGNANT MELANOMAS

P-170 glycoprotein, glutathione and glutathione S-transferases are important in in vitro drug resistance, but their clinical relevance is unclear. Therefore glutathione content, glutathione S-transferase enzyme activity, isoenzyme composition as well as P-170 glycoprotein level were studied in metastases of malignant melanomas of thirteen patients. P-170 glycoprotein and glutathione S-transferases were quantified by immunoblotting with monoclonal antibodies, glutathione S-transferase enzyme activity was measured with 1-chloro-2,4-dinitrobenzene as substrate, and glutathione was assayed by HPLC. Glutathione and glutathione S-transferase enzyme activity were measurable in all samples and mean values were 40+/-7 nmol/mg protein (mean+/-SEM; range: 13-98) and 310+/-72 nmol/min mg protein (range: 15-819), respectively. Glutathione S-transferases present were mainly of class pi (2817+/-402 ng/mg protein); class alpha enzymes were detectable only in one case in low amounts (71 ng/mg protein), and class mu transferases were present in 5 out of the 13 samples (38%; 391+/-206 ng/mg protein). The P-170 glycoprotein plasma membrane located drug efflux pump was found in 8 out of 12 samples (67%). In three samples values were much higher as compared to the other specimens. In the metastatic melanoma of one patient, both high levels of glutathione S-transferase and P-170 glycoprotein were found. Further studies are necessary to reveal whether melanoma tissues containing high levels of P-170 glycoprotein, glutathione S-transferases or a combination of both systems do respond differently towards anti-cancer drug treatment.