[Mechanism of resistance to mitomycin C in a human bladder cancer cell line].
This study was undertaken to determine the mechanism of resistance of a human bladder cancer cell line SCaBER to mitomycin C (MMC). The IC50 value for MMC in SCaBER cells was higher by 2.7 fold by 1-h drug exposure colony formation assay as compared to another bladder cancer cell line J82. NADPH cytochrome P450 reductase and DT-diaphorase activities were significantly lower in SCaBER cells as compared to those of J82 suggesting that relatively resistance of SCaBER cells to MMC may be due to inefficient drug activation. Further support for this conclusion derives from the observation that sensitivities of J82 and SCaBER cells to BMY25282, a MMC analogue with lower quinone reduction potential, were similar. MMC dependent lipid peroxidation (an indicator of oxygen free radical formation) was higher in SCaBER cells than in J82. The activities of anti-oxsidative enzymes GSH peroxidase and catalase did not differ significantly in these cells. These results suggest that resistance of SCaBER cells to MMC may not be due to the reduced free radical formation in these cells. MMC induced DNA interstrand cross-link (ISC) formation was markedly lower in SCaBER cells than in J82. Taken together, these results suggest that SCaBER cell resistance to MMC may be due to the reduced drug activation and ISC formation in these cells.
Xu
B
B
Cancer Hospital, Chinese Academy of Medical Sciences, Beijing.
Sun
Y
Y
Singh
S V
SV
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000473:pathology*
D000903:Antibiotics, Antineoplastic; D004273:DNA, Neoplasm; D016685:Mitomycin; D009251:NADPH-Ferrihemoprotein Reductase; D016660:NAD(P)H Dehydrogenase (Quinone)