Studies of the mode of action of antitumour triazenes and triazines--IV. The metabolism of 1-(4-acetylphenyl)-3,3-dimethyltriazene

Biochem Pharmacol. 1982 May 15;31(10):1887-92. doi: 10.1016/0006-2952(82)90492-0.

Abstract

The metabolism of 1-(4-acetylphenyl)-3,3-dimethyltriazene has been studied in vivo and in vitro in mice. This dimethyltriazene was extensively metabolised in vivo and HPLC analysis of the plasma revealed the presence of two metabolites, the monomethyltriazene, 1-(4-acetylphenyl)-3-methyltriazene, and the arylamine, 4-aminoacetophenone. The dimethyltriazene was also biotransformed in vitro by a 9000 g fraction of mouse liver homogenate to products which were selectively toxic to TLX5 lymphoma cells. HPLC analysis of the products of in vitro metabolism under these conditions showed the presence of the monomethyltriazene but in an amount insufficient to account for the observed cytotoxicity. The monomethyltriazene was itself rapidly biotransformed by a 9000 g fraction of mouse liver homogenate, and by isolated mouse hepatocytes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / metabolism*
  • Antineoplastic Agents / pharmacology
  • Biotransformation
  • Cell Survival / drug effects
  • Female
  • In Vitro Techniques
  • Liver / metabolism
  • Lymphoma / drug therapy
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / drug therapy
  • Triazenes / metabolism*

Substances

  • Antineoplastic Agents
  • Triazenes
  • 1-(4-carboxyethylphenyl)-3,3-dimethyltriazene
  • 1-(4-acetyphenyl)-3,3-dimethyltriazene