Volpato Milène, Seargent Jill, Loadman Paul M, Phillips Roger M
Cancer Research Unit, Tom Connors Cancer Research Centre, University of Bradford, Bradford BD7 1DP, UK.
Eur J Cancer. 2005 Jun;41(9):1331-8. doi: 10.1016/j.ejca.2005.03.014.
Tumour response to Mitomycin C (MMC) is heterogenous and past attempts to predict clinical response based on enzyme activities have proven unsatisfactory. Using in vitro techniques, the aim of this study was to determine if the induction of DNA interstrand cross-links correlated with cellular response and to assess if DNA repair and induction of apoptosis influenced MMC chemosensitivity. Poor correlations were found between sensitivity and both DNA repair and induction of apoptosis suggesting that these processes do not play a major role in determining cellular response to MMC. In contrast, there was good correlation between the induction of DNA interstrand cross-links as determined by the alkaline comet assay and cellular response, suggesting that the biochemical events leading to DNA damage are the key factors that determine cellular response in vitro. Further studies are required to assess whether this approach as a mean of prediction has practical applications in vivo.
肿瘤对丝裂霉素C（MMC）的反应具有异质性，过去基于酶活性预测临床反应的尝试已被证明并不理想。本研究旨在利用体外技术确定DNA链间交联的诱导是否与细胞反应相关，并评估DNA修复和凋亡诱导是否影响MMC的化学敏感性。研究发现敏感性与DNA修复及凋亡诱导之间的相关性较差，这表明这些过程在决定细胞对MMC的反应中并不起主要作用。相比之下，通过碱性彗星试验测定的DNA链间交联诱导与细胞反应之间存在良好的相关性，这表明导致DNA损伤的生化事件是决定体外细胞反应的关键因素。需要进一步研究以评估这种作为预测手段的方法在体内是否具有实际应用价值。
