The role of formaldehyde in methylene dimethanesulphonate-induced DNA cross-links and its relevance to cytotoxicity.
AffiliationPaterson Laboratories, Christie Hospital and Holt Radium Institute, Manchester, M20 9BX (United Kingdom)
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AbstractThe interaction of the antitumour dialkanesulphonate ester, methylene dimethanesulphonate (MDMS) with the DNA of Yoshida sarcoma cells has been studied using the technique of alkaline elution. A marked retention which was reversed by proteolytic treatment indicated the presence of DNA-protein cross-links. A small proteinase-resistant retention was also observed which indicated that a low level of DNA-DNA interstrand cross-links also occurred. Treatment of cells with the amounts of formaldehyde expected by hydrolysis of the drug showed proteinase-reversible DNA-protein cross-linking which on proteolytic removal revealed a small number of single-strand breaks. Thus, MDMS causes both DNA-protein and DNA-DNA interstrand cross-links, the former component being attributed totally to the formaldehyde produced on the drug's hydrolysis. Cell survival data showed formaldehyde to be comparatively non-cytotoxic, providing evidence that DNA-DNA cross-links observable by this technique may be associated with the cytotoxicity of MDMS.
CitationThe role of formaldehyde in methylene dimethanesulphonate-induced DNA cross-links and its relevance to cytotoxicity. 1981, 38 (1):119-28 Chem Biol Interact