Formation of DNA interstrand cross-links as a marker of Mitomycin C bioreductive activation and chemosensitivity

Milène Volpato, Paul M. Loadman, Roger M. Phillips

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1331-1338
Number of pages8
JournalEuropean Journal of Cancer
Volume41
Issue number9
Early online date24 May 2005
DOIs
Publication statusPublished - Jun 2005
Externally publishedYes

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