Formation of DNA interstrand cross-links as a marker of Mitomycin C bioreductive activation and chemosensitivity.
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.
Volpato
Milène
M
Cancer Research Unit, Tom Connors Cancer Research Centre, University of Bradford, Bradford BD7 1DP, UK.
Seargent
Jill
J
Loadman
Paul M
PM
Phillips
Roger M
RM
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D020552:Comet Assay / Q000379:methods; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004249:DNA Damage / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects; D006801:Humans; D007928:Lethal Dose 50; D016685:Mitomycin / Q000494:pharmacology*; D011237:Predictive Value of Tests
D000903:Antibiotics, Antineoplastic; D003432:Cross-Linking Reagents; D016685:Mitomycin