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

P-170 glycoprotein, glutathione and glutathione S-transferases are imp ortant in in vitro drug resistance, but their clinical relevance is un clear. Therefore glutathione content, glutathione S-transferase enzyme activity, isoenzyme composition as well as P-170 glycoprotein level w ere 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 e nzyme activity was measured with 1-chloro-2,4-dinitrobenzene as substr ate, 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 o f the 13 samples (38%; 391+/-206 ng/mg protein). The P-170 glycoprotei n plasma membrane located drug efflux pump was found in 8 out of 12 sa mples (67%). In three samples values were much higher as compared to t he other specimens. In the metastatic melanoma of one patient, both hi gh levels of glutathione S-transferase and P-170 glycoprotein were fou nd. Further studies are necessary to reveal whether melanoma tissues c ontaining high levels of P-170 glycoprotein, glutathione S-transferase s or a combination of both systems do respond differently towards anti -cancer drug treatment.