The effect of methylene dimethanesulphonate (MDMS) on the conformation of DNA and its dependence on base composition

The interaction of the alkanesulphonate, methylene dimethanesulphonate (MDMS) with DNA has been studied. Thermal denaturation studies on mixtures of MDMS and DNA showed a dose-dependent decrease of the melting temperature midpoint (Tm) of the DNA. In addition, an irreversible decrease in ultraviolet absorption (hypochromism) preceded the hyperchromic shift, the magnitude of the former being linearly related to both the relative concentration of MDMS and the G-C content of the DNA used. Neither the reduction in melting temperature nor the initial UV absorption decrease occurred after dialysis of the reaction mixture. Equimolar proportions of the hydrolysis products of MDMS did not give the same effects as observed with the unhydrolysed agent. A similar hypochromism followed by strand separation occurs when DNA is allowed to stand with MDMS at room temperature, the time of subsequent strand separation being related to the treatment level of the drug. A weak association of MDMS with DNA is considered to be involved resulting in a local compression of the helical structure in the vicinity of the G-C pairs. It is suggested that this conformational change may act as a substrate for repair enzymes in vivo.