PMID: 10260Oct 15, 1976

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

International Journal of Cancer. Journal International Du Cancer
F OeschH R Glatt

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.

References

Nov 15, 1975·FEBS Letters·P BentleyA Tsugita
Feb 9, 1976·Biochemical and Biophysical Research Communications·P G WislockiA H Conney
Oct 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·F J WiebelM J Coon
Feb 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·E HubermanV Gelboin
Jan 1, 1975·Annual Review of Biochemistry·C Heidelberger
Sep 16, 1975·Biochemical and Biophysical Research Communications·C MalaveilleP Sims
Nov 15, 1975·International Journal of Cancer. Journal International Du Cancer·H R GlattS Garattini
Aug 1, 1975·Proceedings of the National Academy of Sciences of the United States of America·A W WoodD M Jerina
Nov 15, 1975·FEBS Letters·P Bentley, F Oesch
Aug 1, 1973·Proceedings of the National Academy of Sciences of the United States of America·B N AmesF D Lee
Apr 15, 1974·Biochemical Pharmacology·F OeschH Fahrlaender
Mar 1, 1973·Proceedings of the National Academy of Sciences of the United States of America·B N AmesW E Durston
Jan 1, 1974·Advances in Cancer Research·P Sims, P L Grover

Citations

Dec 30, 1977·Archives of Toxicology·P BentleyH R Glatt
Sep 1, 1979·Mutation Research·M HollsteinW W Nichols
Jan 1, 1990·Mutation Research·M D WatersH E Brockman
Oct 1, 1982·Mutation Research·G M SeixasW G Thilly
Feb 1, 1980·British Journal of Industrial Medicine·I F Purchase
Apr 1, 1984·Food Additives and Contaminants·D J Tweats
Jun 1, 1980·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·W L AlworthT Viswanathan
Jan 1, 1979·Drug Metabolism Reviews·F W Deckert
Jun 1, 1987·Analytical Biochemistry·A ZhiriG Siest
Mar 21, 1977·Biochemical and Biophysical Research Communications·C MalaveilleH Bartsch
Nov 14, 1978·Biochemical and Biophysical Research Communications·L M CalleJ Jollick
Jan 1, 1982·Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes·W M Draper, J C Street
Jan 1, 1984·Acta Pharmacologica Et Toxicologica·F Oesch

Related Concepts

Benz(a)Anthracenes
Benzpyrene
9,10-Epoxypalmitic Acid Hydrase
Hydro-Lyases
Microsomes, Liver
NADP
Salmonella typhimurium LT2

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

The Tendon Seed Network

Tendons are rich in the extracellular matrix and are abundant throughout the body providing essential roles including structure and mobility. The transcriptome of tendons is being compiled to understand the micro-anatomical functioning of tendons. Discover the latest research pertaining to the Tendon Seed Network here.

Myocardial Stunning

Myocardial stunning is a mechanical dysfunction that persists after reperfusion of previously ischemic tissue in the absence of irreversible damage including myocardial necrosis. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Incretins

Incretins are metabolic hormones that stimulate a decrease in glucose levels in the blood and they have been implicated in glycemic regulation in the remission phase of type 1 diabetes. Here is the latest research.

Chromatin Regulation and Circadian Clocks

The circadian clock plays an important role in regulating transcriptional dynamics through changes in chromatin folding and remodelling. Discover the latest research on Chromatin Regulation and Circadian Clocks here.

Long COVID-19

“Long Covid-19” describes illness in patients who are reporting long-lasting effects of the SARS-CoV-19 infection, often long after they have recovered from acute Covid-19. Ongoing health issues often reported include low exercise tolerance and breathing difficulties, chronic tiredness, and mental health problems such as post-traumatic stress disorder and depression. This feed follows the latest research into Long Covid.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.