OVEREXPRESSION OF HUMAN MUTT HOMOLOG GENE MESSENGER-RNA IN RENAL-CELLCARCINOMA - EVIDENCE OF PERSISTENT OXIDATIVE STRESS IN CANCER

Data regarding oxidatively modified DNA bases suggest that cancer cell s are more exposed to oxidative stress than adjacent non-tumorous tiss ue. This novel concept may contribute to the understanding of certain aspects of tumor biology such as activated transcription factors, gene tic instability, chemotherapy-resistance and metastasis. We therefore tested this concept in human renal-cell carcinomas (RCCs) by evaluatin g the expression of hMTHl, an enzyme preventing the misincorporation i nto DNA of 8-oxo-dGTP (8-oxo-7,8-dihydrodeoxyguanosine triphosphate), an oxidized form of dGTP in the nucleotide pool. The expression of hMT Hl messenger RNA (mRNA) in RCC was significantly higher than that in a djacent non-tumorous kidney. Moreover, advanced-stage tumors showed si gnificantly higher hMTHl mRNA expression than early-stage tumors, and there was a modest linear correlation between hMTHl expression and c-m yc expression. The results provide logical support for the concept of ''persistent oxidative stress in cancer'' and suggest a role of hMTHl mRNA level as a prognostic marker. (C) 1996 Wiley-Liss, Inc.