The bioactivation of 1,2-dibromoethane in rat hepatocytes: deuterium isotope effect.

Abstract:

:The metabolism and genotoxicity of 1,2-dibromoethane (EDB) and its deuterium substituted analog ( d4EDB ) were studied in isolated rat hepatocytes. There was a marked isotope effect on the metabolism of EDB by hepatocytes. This was due to decreased microsomal oxidation of d4EDB . Cytosolic metabolism of EDB, as measured by bromide ion release, was unaffected by deuterium substitution. The genotoxicity of the two analogs was assessed by assaying for the presence of EDB induced single-strand breaks in DNA. As measured by the alkaline elution technique, both compounds caused DNA single-strand breaks when incubated at a concentration of 0.1 mM with hepatocytes. No difference in the degree of DNA damage could be demonstrated between hepatocytes incubated with EDB or d4EDB . These data suggest that the GSH transferase mediated metabolism of EDB is responsible for the genotoxic effects of EDB observed in hepatocytes.

journal_name

Chem Biol Interact

authors

White RD,Petry TW,Sipes IG

doi

10.1016/0009-2797(84)90063-2

subject

Has Abstract

pub_date

1984-04-01 00:00:00

pages

225-33

issue

1-2

eissn

0009-2797

issn

1872-7786

pii

0009-2797(84)90063-2

journal_volume

49

pub_type

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