Prevention of benzo(a)pyrene-induced mutagenicity by homogeneous epoxide hydratase.

Abstract:

:Benzo(a)pyrene and benz(a) anthrancene which, in contrast to the K-region epoxides benzo(a)pyrene 4,5-oxide and benz(a)anthracene 5,6-oxide, are not mutagenic to Salmonella typhimurium TA 1537 in the absence of mammalian enzyme preparations, were activated by liver microsomes from C3H mice, which had not received any pretreatment, to mutagens reverting this tester strain to histidine prototrophy. Addition of epoxide hydratase inhibitors greatly increased this mutagenicity and addition of pure epoxide hydratase reduced it by more than 95% down to the range of spontaneous mutations as observed in absence of any added mutagen. This demonstrates than the metabolic pathway responsible for the mutagenicity of both polycyclic hydrocarbons observed in this system proceeds entirely via an epoxidation pathway and that the responsible metabolites are epoxides or species arising from them. Moreover, further metabolism by epoxide hydratase does not lead to produce contributing to the mutagenicity observed with the tester strain used. Finally, the epoxides relevant for the observed mutagenicity are substrates for epoxide hydratase; indeed, modest amounts of the pure enzyme can prevent the mutagenic effect.

journal_name

Int J Cancer

authors

Oesch F,Bentley P,Glatt HR

doi

10.1002/ijc.2910180408

keywords:

subject

Has Abstract

pub_date

1976-10-15 00:00:00

pages

448-52

issue

4

eissn

0020-7136

issn

1097-0215

journal_volume

18

pub_type

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