Metabolic activation and detoxification of bromobenzene leading to cytotoxicity

Serrine Lau, G. D. Abrams, V. G. Zannoni

Research output: Contribution to journalArticle

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Abstract

Two hepatic microsomal metabolic pathways of bromobenzene, o-bromophenol (via a nontoxic 2,3-epoxide) and p-bromophenol (via a toxic 3,4-epoxide) were studied in C57BL/J and Balb/cJ mice. A significant quantitative difference was found; in particular, the constitutive activity of the toxic 3,4-epoxide pathway. The specific activity in BALB/cJ mice was 93.4 nmol/min/100 mg of protein compared to 47.5 nmol/min/100 mg of protein in the C57BL/J mice. In contrast, no significant difference was found in the 2,3-epoxide pathway in either strain. In addition, the major detoxifying pathways of the epoxides; e.g. microsomal epoxide hydrase and cytoplasmic glutathione transferase were determined in the BALB/cJ and C57BL/J mice and no significant differences in these activities were found. Furthermore, there were no significant differences in the quantity of the dihydrodiol or mercapturic acid products in the two strains of mice. A comparative investigation of hepatic centrolobular necrosis and pharmacodynamic blood profile after bromobenzene administration was undertaken in these mice. Extensive hepatic necrosis occurred in 90% of the BALB/cJ mice, whereas 80% of C57BL/J mice had no pathological changes. Furthermore, the rate of disappearance of bromobenzene in blood of individual mice indicated a half-life of 28 ± 5.3 min for BALB/cJ and 60 ± 6.4 min for C57BL/J mice. This study furnishes excellent correlation between in vivo hepatic necrosis, rate of disappearence of bromobenzene in blood and in vitro enzymatic formation of p-bromophenol via 3,4-epoxidation.

Original languageEnglish (US)
Pages (from-to)703-708
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume214
Issue number3
StatePublished - 1980
Externally publishedYes

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Epoxy Compounds
Inbred C57BL Mouse
Necrosis
Poisons
Liver
Epoxide Hydrolases
Acetylcysteine
Metabolic Networks and Pathways
Glutathione Transferase
Half-Life
bromobenzene
Metabolic Activation
Proteins
4-bromophenol

ASJC Scopus subject areas

  • Pharmacology

Cite this

Metabolic activation and detoxification of bromobenzene leading to cytotoxicity. / Lau, Serrine; Abrams, G. D.; Zannoni, V. G.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 214, No. 3, 1980, p. 703-708.

Research output: Contribution to journalArticle

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