Evaluation of epichlorohydrin (ECH) genotoxicity. Microsomal epoxide hydrolase-dependent deactivation of ECH mutagenicity in Schizosaccharomyces pombe in vitro

A. M. Rossi, L. Migliore, N. Loprieno, M. Romano, M. Salmona

Research output: Contribution to journalArticlepeer-review

Abstract

The mutagenic effect of epichlorohydrin (ECH) on the yeast Schizosaccharomyces pombe was studied in vitro in the presence of mouse-liver S9 mix and microsomal and cytosolic fractions. The incubations were always performed in the absence of NADPH-generating systems. S9 mix and microsomes from phenobarbital-pretreated mice significantly reduced ECH mutagenicity, whereas the cytosol did not result in any deactivating effect. The various protein contents of the subcellular fractions were not involved in any scavenger effect as regards ECH mutagenic activity. Moreover, the addition of reduced glutathione to the incubation mixtures indicated that it did not play an important role, either per se or through the enzyme(s) glutathione-S-epoxide transferase(s), in preventing ECH genotoxicity. Our results suggest that microsomal epoxide hydrolase(s) represents the major step in the detoxifying pathway of ECH. These observations were supported by measurements of the specific epoxide hydrolase activity in the various fractions on the same substrate.

Original languageEnglish
Pages (from-to)41-52
Number of pages12
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume109
Issue number1
DOIs
Publication statusPublished - 1983

ASJC Scopus subject areas

  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

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