Mechanism of differential sensitivity of human bladder cancer cells to mitomycin C and its analogue.
Mechanism of differential sensitivity of human bladder cancer cells to mitomycin C and its analogue.
复制标题
人膀胱癌细胞对丝裂霉素C及其类似物的差异敏感性机制。
DOI：
10.1038/bjc.1994.46
复制
发表时间：
1994
影响因子：
8.8
通讯作者：
Singh,SV
中科院分区：
文献类型：
--
作者：
Xu,BH;Gupta,V;Singh,SV
本研究旨在探讨人膀胱癌细胞株J82和SCABER对丝裂霉素C及其类似物BMY-25067的差异敏感性机制(S)。丝裂霉素C和BMY 25067对SCABER细胞的IC50值分别是J82的5倍和4倍。在两种细胞系中，BMY 25282和BMY 25067在摩尔基础上的细胞毒性明显高于丝裂霉素C。J82细胞的NADPH细胞色素P450还原酶和DT黄递酶活性明显高于SCABER细胞，提示SCABER细胞对丝裂霉素C和25067的敏感性较低，可能是药物活化不足所致。这一结论得到以下观察的支持，即Bmy 25282的苯二酚还原潜力低于丝裂霉素C和Bmy 25067，在这些细胞系中没有显著差异。未观察到药物敏感性、氧自由基形成和抗氧化酶水平之间的相关性。这些结果表明，SCABER细胞对丝裂霉素C或25067的敏感性相对较低，可能与不同的氧自由基的形成无关。丝裂霉素C诱导的DNA链间交联(ISC)在SCABER细胞系中明显低于J82细胞系。然而，scaber细胞系中ISC频率的降低是药物激活不足的结果，还是由于受损DNA修复增加的结果，仍有待观察。
This study was undertaken to elucidate the mechanism (s) of differential sensitivity of human bladder cancer cell lines J82 and SCaBER to mitomycin C (MMC) and its analogue, BMY 25067. The IC50 values for MMC and BMY 25067 in the SCaBER cell line were respectively 5-and 4-fold higher than in J82. BMY 25282 and BMY 25067 were significantly more cytotoxic, on a molar basis, than MMC in both the cell lines. NADPH cytochrome P450 reductase and DT diaphorase activities were significantly higher in the J82 cell line than in SCaBER, suggesting that relatively lower sensitivity of the SCaBER cell line to MMC and BMY 25067 may be due to deficient drug activation. This conclusion was supported by the observation that IC50 values for BMY 25282, which has lower quinone reduction potential than MMC and BMY 25067, did not differ significantly in these cell lines. A correlation between drug sensitivity, oxyradical formation and levels of antioxidative enzymes was not observed. These results suggest that the relatively lower sensitivity of SCaBER cells to MMC or BMY 25067 may be independent of differential oxyradical formation. MMC-induced DNA interstrand cross-link (ISC) formation was markedly lower in the SCaBER cell line than in J82. However, it remains to be seen if the reduced ISC frequency in the SCaBER cell line is a consequence of deficient drug activation or results from increased repair of the damaged DNA.