Biomaterial Database

Prostaglandin H synthase-dependent mutagenic activation of benzidine in a Salmonella typhimurium Ames tester strain possessing elevated N-acetyltransferase levels. 1989

P D Josephy, and A L Chiu, and T E Eling

Guelph-Waterloo Centre for Graduate Work in Chemistry, Department of Chemistry and Biochemistry, University of Guelph, Ontario, Canada.

Watanabe and colleagues (Biochem. Biophys. Res. Commun. 147: 974-979, 1987) have constructed plasmid-containing derivatives of Salmonella typhimurium Ames tester strain TA1538 with high levels of acetyltransferase activities. In this paper, we describe the mutagenic response of one of these strains, TA1538/1,8-DNP6 (pYG 121), to the bladder carcinogen benzidine and other arylamines. Strain TA1538/1,8-DNP6 (pYG 121) was far more sensitive to benzidine than any previous tester strain, following metabolism of the aromatic amine by hamster hepatic S9, ram seminal vesicle microsomal preparation (RSVM), or purified prostaglandin synthase. Therefore, bacterial acetyltransferase-dependent metabolism of a proximate mutagen is implicated in each of these systems. The mechanism of RSVM-dependent activation of benzidine was examined further. The arachidonic acid-independence and indomethacin insensitivity previously noted with strain TA98 were also observed with the new tester strain. We confirmed that prostaglandin H synthase is the enzyme activity responsible for activation of benzidine by RSVM. Purified prostaglandin H synthase holoenzyme, or apoenzyme reconstituted with heme, supported benzidine activation. However, apoenzyme reconstituted with manganese protoporphyrin IX, which yields enzyme having cyclooxygenase activity but not peroxidase activity, was inactive. Addition of catalase inhibited, and addition of exogenous hydrogen peroxide increased, RSVM-mediated benzidine mutagenicity. We propose that hydrogen peroxide released by the tester strain bacteria (rather than arachidonic acid-derived peroxide) is the oxidizing agent which supports prostaglandin H synthase peroxidase activity in Ames test systems.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008861	Microsomes	Artifactual vesicles formed from the endoplasmic reticulum when cells are disrupted. They are isolated by differential centrifugation and are composed of three structural features: rough vesicles, smooth vesicles, and ribosomes. Numerous enzyme activities are associated with the microsomal fraction. (Glick, Glossary of Biochemistry and Molecular Biology, 1990; from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)	Microsome
D008862	Microsomes, Liver	Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.	Liver Microsomes,Liver Microsome,Microsome, Liver
D009152	Mutagenicity Tests	Tests of chemical substances and physical agents for mutagenic potential. They include microbial, insect, mammalian cell, and whole animal tests.	Genetic Toxicity Tests,Genotoxicity Tests,Mutagen Screening,Tests, Genetic Toxicity,Toxicity Tests, Genetic,Genetic Toxicity Test,Genotoxicity Test,Mutagen Screenings,Mutagenicity Test,Screening, Mutagen,Screenings, Mutagen,Test, Genotoxicity,Tests, Genotoxicity,Toxicity Test, Genetic
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D011451	Prostaglandin-Endoperoxide Synthases	Enzyme complexes that catalyze the formation of PROSTAGLANDINS from the appropriate unsaturated FATTY ACIDS, molecular OXYGEN, and a reduced acceptor.	Fatty Acid Cyclo-Oxygenase,PGH Synthase,Prostaglandin H Synthase,Prostaglandin Synthase,Prostaglandin-Endoperoxide Synthase,Arachidonic Acid Cyclooxygenase,Cyclo-Oxygenase,Cyclooxygenase,Cyclooxygenases,Hydroperoxide Cyclase,PGH2 Synthetase,Prostaglandin Cyclo-Oxygenase,Prostaglandin Cyclooxygenase,Prostaglandin Endoperoxide Synthetase,Prostaglandin G-H Synthase,Prostaglandin H2 Synthetase,Prostaglandin Synthetase,Cyclase, Hydroperoxide,Cyclo Oxygenase,Cyclo-Oxygenase, Fatty Acid,Cyclo-Oxygenase, Prostaglandin,Cyclooxygenase, Arachidonic Acid,Cyclooxygenase, Prostaglandin,Endoperoxide Synthetase, Prostaglandin,Fatty Acid Cyclo Oxygenase,G-H Synthase, Prostaglandin,Prostaglandin Cyclo Oxygenase,Prostaglandin Endoperoxide Synthases,Prostaglandin G H Synthase,Synthase, PGH,Synthase, Prostaglandin,Synthase, Prostaglandin G-H,Synthase, Prostaglandin H,Synthase, Prostaglandin-Endoperoxide,Synthases, Prostaglandin-Endoperoxide,Synthetase, PGH2,Synthetase, Prostaglandin,Synthetase, Prostaglandin Endoperoxide,Synthetase, Prostaglandin H2
D006224	Cricetinae	A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.	Cricetus,Hamsters,Hamster
D000123	Acetyltransferases	Enzymes catalyzing the transfer of an acetyl group, usually from acetyl coenzyme A, to another compound. EC 2.3.1.	Acetyltransferase
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001560	Benzidines	Very toxic industrial chemicals. They are absorbed through the skin, causing lethal blood, bladder, liver, and kidney damage and are potent, broad-spectrum carcinogens in most species.	Bianilines,Biphenyldiamines