Covalent interaction of dehydroretronecine, a carcinogenic metabolite of the pyrrolizidine alkaloid monocrotaline, with cysteine and glutathione.

Abstract

The covalent interaction of dehydroretronecine, a carcinogenic metabolite of the pyrrolizidine alkaloid monocrotaline, with cysteine and glutathione, has been investigated. Dehydroretronecine was allowed to react with cysteine and glutathione in an in vitro system of phosphate buffer solutions. The reaction products were identified structurally by chromatographic, nuclear magnetic resonance, infrared, ultraviolet, and mass-spectral analysis. These data indicate that the reaction products are the sulfhydryl-linked 7-thiocysteine-dehydroretronecine and 7-thioglutathione-dehydroretronecine. Active alkylation of sulfhydryl groups is a possible mechanism by which these alkaloids interact with cellular components.