Comparative studies of DNA cross-linking reactions following methylene dimethanesulphonate and its hydrolytic product, formaldehyde.

The technique of alkaline elution was employed to study the interactions of methylene dimethane sulphonate (MDMS) and formaldehyde (HCHO) with DNA from Yoshida lymphosarcoma cells treated with these agents. MDMS and HCHO produced a proteinase sensitive filter retention which indicated the presence of DNA-protein cross-links. MDMS also produced some proteinase K-resistant filter retention which was believed to indicate DNA-interstrand cross-linking, whilst only single-strand breaks could be detected following treatment with HCHO. Co-incubation with semicarbazide prevented all DNA-protein cross-links induced by MDMS and HCHO as well as single-strand breaks, most obvious following HCHO treatment. Semicarbazide also reduced HCHO-induced cytotoxicity in the Yoshida lymphosarcoma cell line, while no significant alteration in MDMS-induced cytotoxicity was observed. These results suggest that HCHO-induced DNA-protein cross-links and single-strand breaks do not contribute to MDMS-induced cytotoxicity, and therefore the small but significant level of MDMS-induced DNA-interstrand cross-links is the most likely cytotoxic lesion of this agent.