EXPRESSION OF NAD(P)H-QUINONE OXIDOREDUCTASE AND GLUTATHIONE-S-TRANSFERASE-ALPHA AND GLUTATHIONE-S-TRANSFERASE-PI IN HUMAN RENAL-CELL CARCINOMA AND IN KIDNEY CANCER-DERIVED CELL-LINES

NAD(P)H:quinone oxidoreductase (NQOR) and glutathione S-transferases ( GST) are enzymes of interest in cell defence and drug resistance. Rela tive levels of NQOR mRNA in renal cell carcinomas were 28 +/- 24% (n=2 1) of those in nonneoplastic tissue and the enzyme activity decreased from 41 +/- 39 to 18 +/- 27 mU/mg protein (n=23). In three of the case s, there was no measurable NQOR enzyme activity at all, indicating a p olymorphism in the population for this gene. Relative GST-alpha mRNA l evels in the tumours were on average 6 +/- 6% (n=22) of the control va lue, whereas for GST-pi mRNA smaller decreases as well as increases we re found in the tumours as compared to control tissue, but, on average , the level remained unchanged. Overall GST activity measured with CDN B as a substrate was 152 +/- 157 mU/mg protein in tumour tissue and 34 2 +/- 177 mU/mg protein in non-neoplastic tissue (n=23). In all kidney tumour-derived cell lines NQOR mRNA was strongly expressed and on a p er protein basis NQOR activity was about 10-fold higher than in the ki dney tumour samples. GST-pi but not GST-alpha mRNA was also present. T otal GST enzyme activities in these cell lines were similar to those i n kidney tumour samples. HepG2 cells exhibited expression of NQOR and GST-alpha; GST-pi was not detectable. NQOR activity in HepG2 was about four-fold higher than in kidney-derived cell lines. Thus, NQOR and GS T-alpha are both down-regulated in renal carcinoma, but their expressi on diverges in carcinoma cell lines.