Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antitumor agents 5-(3,3-dimethyl-1-triazenyl)imidazole-4-carboxamide (DIC) and 5-[3,3-bis(2-chloroethyl)-1-triazenyl]imidazole-4-carboxamide (BIC) are substrates for NADPH-requiring microsomal enzymes of mouse liver. The products of DIC oxidation are 5-aminoimidazole-4-carboxamide (AIC) and formaldehyde. Those for BIC are AIC and, presumably, 2-chloroacetaldehyde. For DIC, the reaction has a pH optimum of 9.0; and the Michaelis constant (Km) is 0.25 mM. At lower pH values, the Km is not greatly increased; but there is a sharp rise in the Km values above pH 9.0. For the enzyme-catalyzed production of AIC from BIC, the pH optimum is 7.5; the Km value for BIC is 0.47 mM. Of a variety of tissues tested for enzymatic activity, only liver accomplishes the conversion of DIC and BIC to AIC. Most of the activity in the liver is located in the microsomal fraction, although detectable activity is present in washed mitochondria. For liver microsomes, the rate of reaction for BIC is greater than that for DIC, but apparently neither rate is fast enough to allow extensive metabolism of large doses of these agents.
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PMID:Microsomal metabolism of triazenylimidazoles. 24 85

L1210 leukemia was transplanted serially in CDF(1) mice treated with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DIC, NSC 45388). After four different lines (C lines) had been treated for several generations, a marked increase in survival time of untreated mice was observed. In contrast, mice treated with DIC or immunosuppressed with cyclophosphamide succumbed earlier with generalized leukemia. Furthermore, a C line showed unusually high sensitivity to chemotherapeutic treatment with 1,3 bis(2-chloroethyl)-1-nitrosourea. The data suggest that C lines acquired strong antigenicity for CDF(1) and DBA/2 hosts. DIC treatment may have selected highly antigenic variants or induced somatic mutations resulting in the appearance of strong new transplantation antigen(s).
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PMID:Immunological alteration of leukemic cells in vivo after treatment with an antitumor drug. 527 45