Accession Number : AD0482948

Title :   RADIOMIMETIC AGENTS. II. THE ENZYMATIC TRANSFORMATION OF SOME NITROGEN MUSTARDS IN THE PRESENCE OF CARBON DIOXIDE: IMPLICATIONS IN RESPIRATION.

Descriptive Note : Rept. for May 63-Jun 65,

Corporate Author : CHEMICAL RESEARCH AND DEVELOPMENT LABS EDGEWOOD ARSENAL MD

Personal Author(s) : Williamson, Charles E.

Report Date : DEC 1965

Pagination or Media Count : 29

Abstract : In vitro kinetic studies in various biological media have led to the observation of an enzyme in blood serum that catalyzes the reaction between secondary nitrogen mustards and carbon dioxide to form substituted oxazolidinones. This reaction results in the very rapid degradation of certain nitrogen mustards frequently employed in cancer chemotherapy. Upon contact with blood or animal tissues, agents such as Degranol and Nor-HN2 are immediately transformed into products incapable of undergoing typical alkylation reactions. In light of these observations pharmacological data thus far collected on these nitrogen mustards must be reevaluated. Interpretation of the kinetic data obtained indicates that the enzyme catalyzes carbamate formation - a reaction of importance for the transport of carbon dioxide in blood. It is proposed that a normal metabolic function of this enzyme is to catalyze this reaction during respiration. (Author)

Descriptors :   *BIOCHEMISTRY), (*NITROGEN MUSTARDS, IN VIVO ANALYSIS, DRUGS, PHARMACOLOGY, CHEMICAL REACTIONS, BLOOD, BLOOD ANALYSIS, BIOASSAY, IN VITRO ANALYSIS, CARBON DIOXIDE, DEGRADATION, ENZYMES, BIOLOGICAL PRODUCTS, CHEMOTHERAPEUTIC AGENTS, TRANSFORMATIONS, ALKYLATION, CANCER, RESPIRATION, METABOLISM, CARBAMIC ACID.

Subject Categories : Biochemistry
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE