title: The role of formaldehyde in methylene dimethanesulphonate-induced DNA cross-links and its relevance to cytotoxicity.
abstract: The 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.
mesh_terms: D000477:Alkylating Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D004273:DNA, Neoplasm / Q000378:metabolism*; D005557:Formaldehyde / Q000494:pharmacology*; D008741:Methyl Methanesulfonate / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D012517:Sarcoma, Yoshida / Q000378:metabolism
chemical_list: D000477:Alkylating Agents; D004273:DNA, Neoplasm; C002538:methylene dimethanesulfonate; D005557:Formaldehyde; D008741:Methyl Methanesulfonate