Studies with alkylating esters—II: A chemical interpretation through metabolic studies of the antifertility effects of ethylene dimethanesulphonate and ethylene dibromide

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Abstract

The metabolism of 1,2-14C-ethylene dimethanesulphonate (EDS) has been followed in the rat and mouse and compared with that of 1,2-14C-ethylene dibromide (EDB). EDS is excreted unchanged in urine together with S-(2-hydroxyethyl)-cysteineN-acetate and S-(2-hydroxyethyl)-cysteine-N-acetate-S-oxide. EDB is not excreted unchanged but is metabolised mainly to S-(2-hydroxyethyl)-cysteine and its N-acetate.

The distribution of radioactive label in mouse tissues is different for both compounds which may indicate a difference in the origin of cysteinal units for alkylation. Both ethylene dimethanesulphonate and ethylene dibromide react efficiently in vitro with SH containing compounds by a reaction analogous to the “sulphur stripping” action of Myleran, although the metabolism of EDS and EDB would not indicate such a reaction takes place in vivo. The antispermatogenic actions of EDS differ from those of its homologues, such as Myleran, but show some resemblance to those of EDB. These effects of EDS and EDB may indicate that both compounds have latent “mustard-like” activity, and this possibility is discussed in terms of the pharmacological effects produced by EDS and its chemical reactions with nucleophiles.

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