Covalent binding of haloethylenes

Abstract

Halogenated ethylenes are metabolized to reactive intermediates which covalently bind to different cellular targets. Vinyl chloride and vinyl bromide metabolites bind to DNA, preferably to N-7 of deoxyguanosine. With RNA, 1,N6-ethenoadenosine and, 3,N4-ethenocytidine moieties are formed. All the haloethylenes in which this effect has been studied form metabolites capable of alkylating proteins, preferably at free sulfhydryl groups. Also, there is alkylation by haloethylene metabolites of cellular coenzymes. An observed increased exhalation of acetone by rats exposed to different haloethylenes can possibly be explained by alkylation of cytosolic coenzyme A. Such metabolic effects may serve as an indicator for reactive metabolite formation in vivo and should be more investigated.