METHYLATION OF CYSTEINE IN HEMOGLOBIN FOLLOWING EXPOSURE TO METHYLATING AGENTS

Google Scholar
  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (6) , 2514-2517
Abstract
In addition to reacting with biologically important nucleophilic sites in DNA, alkylating agents also interact with amino acids in proteins. Measurement of the extent of formation of these alkyl amino acids may be used as a means of determining exposure to these compounds. The degree of S-methylation of cysteine in Hb was studied following in vivo exposure of rats to [the carcinogens] methyl methanesulfonate, dimethylnitrosamine and 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide. A linear dose-response curve was observed for methyl methanesulfonate over a 100-fold dose range. For dimethylnitrosamine, there was a threshold of doses where no methylation could be detected, and a curved dose-response curve was obtained. At high doses, the degree of methylation of Hb cysteine was 7-fold lower than that with methyl methanesulfonate. In vivo, no alkylation could be observed with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide; the existence of naturally occurring S-methylcysteine in the rat Hb may have overshadowed small increases in alkylation arising from exposure to this compound. The natural occurrence of S-methylcysteine was studied and amounts ranging from 5.6 nmol/g globin (hamster) to 481 nmol/g globin (partridge) were observed. The reason for its occurrence is unknown but is under investigation.