Mechanism of metabolic activation of chloroform by rat liver microsomes

Lance R. Pohl, Jackie L. Martin, John W. George

Research output: Contribution to journalArticlepeer-review

Abstract

In this investigation, we attempted to determine if reactive metabolites other than phosgene (COCl2) are involved in the metabolic activation of chloroform (CHCl3) in rat liver microsomes. This problem was approached by determining whether the formation of COCl2 can account for the metabolism of CHCl3 to covalently bound product, carbon dioxide (CO2), and chloride ion (Cl-). It was found that the levels of covalent binding of [14CHCl3 and [14C]CO2 formation decreased proportionately when [14C]COCl2 was trapped as 2-oxothiazolidine-4-carboxylic acid by the addition of cysteine to the incubation mixture. The amount of this product corresponded closely to the sum of the decreases in covalent binding and CO2 formation. [36Cl]Chloride was formed from [36Cl]CHCl3 under the same conditions that produced COCl2 from CHCl3. In addition, when 14C-, 3H-, or 36Cl-labelled CHCl3 was incubated with liver microsomes under a variety of conditions, only the 14C-label was appreciably bound irreversibly to microsomal protein. These results support the view that COCl2 is the major, if not the only, reactive metabolite formed from CHCl3 in rat liver microsomes.

Original languageEnglish (US)
Pages (from-to)3271-3276
Number of pages6
JournalBiochemical Pharmacology
Volume29
Issue number24
DOIs
StatePublished - Dec 15 1980

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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