Biomaterial Database

Benzo[a]pyrene metabolism and macromolecular binding in strains of Ah responsive and Ah non-response mice. 1980

J B Vaught, and H L Gurtoo, and N B Parker, and L A Hauser

Using liver microsomes as the enzyme source in in vitro assays, benzo[a]pyrene (BP) metabolism was studied in eight inbred strains of mice (C57BL/6J, DBA/2HaD, BALB/cCR, AKR/Sn, RF/J, CBA/J, C57L/J and 129/J). BP metabolite formation was monitored by high pressure liquid chromatography (HPLC) and by following aryl hydrocarbon hydroxylase (AHH) activity. Other parameters measured in cluded the formation of alkali-extractable radioactivity due to [3H] BP metabolites, microsomal protein binding, DNA binding and epoxide hydrase activity. The induction of BP metabolism and binding to macromolecules was studied after treatment of animals with phenobarbital (PB) or 3-methylcholanthrene (MC). Four of the mouse strains (C57BL/6J, BALB/cCr, CBA/J and C57L/J) were highly inducible with respect to liver AHH when pretreated with MC. The induction of AHH by MC in these strains correlated well with the radioactive metabolites of [3H] BP remaining in the alkali extract derived from the AHH assay mixture and with the increased binding of [3H] BP to microsomal protein and DNA. In addition to the eight strains listed above, eight recombinant inbred lines showed a positive correlation between AHH induction and induction of DNA-binding metabolites. PB pretreatment resulted in less than two-fold induction of AHH and alkali-extractable radioactivity. However, DNA and microsomal protein binding were induced by PB pretreatment more than AHH. Ratios of MC-induced/basal activity for BP-phenols were very similar to induction ratios of AHH activity determined by the fluorometric method. BP-quinone formation was induced to the same extent as phenols. This relationship did not hold for dihydrodiol formation; dihydrodiol induction was often higher than AHH or phenol induction. For MC-pretreated mice, dihydrodiol induction, as determined by HPLC, did not parallel macromolecular binding induction as closely as did AHH. For PB-pretreated mice, dihydrodiol induction was as poor as indicator of binding induction as AHH. Epoxide hydrase activity, using styrene oxide as substrate, was induced markedly by PB-pretreatment, but very little by MC-pretreatment. Epoxide hydrase induction did not parallel BP-dihydrodiol induction when microsome preparations from MC- or PB-treated mice were used. These data suggest this enzyme is not rate limiting in this system.

UI	MeSH Term	Description	Entries
D008748	Methylcholanthrene	A carcinogen that is often used in experimental cancer studies.	20-Methylcholanthrene,3-Methylcholanthrene,20 Methylcholanthrene,3 Methylcholanthrene
D008815	Mice, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.	Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
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
D010634	Phenobarbital	A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.	Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D011506	Proteins	Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.	Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
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
D001189	Aryl Hydrocarbon Hydroxylases	A large group of cytochrome P-450 (heme-thiolate) monooxygenases that complex with NAD(P)H-FLAVIN OXIDOREDUCTASE in numerous mixed-function oxidations of aromatic compounds. They catalyze hydroxylation of a broad spectrum of substrates and are important in the metabolism of steroids, drugs, and toxins such as PHENOBARBITAL, carcinogens, and insecticides.	Microsomal Monooxygenases,Xenobiotic Monooxygenases,Hydroxylases, Aryl Hydrocarbon,Monooxygenases, Microsomal,Monooxygenases, Xenobiotic
D001580	Benzopyrenes	A class of chemicals that contain an anthracene ring with a naphthalene ring attached to it.	Benzpyrene