Steroselective metabolism of dizen(a,h)anthracene to trans-dihydrodiols and their activation to bacterial mutagens
- Univ. of Mainz (West Germany)
Dibenz(a,h)anthracene (DBA), a carcinogenic, polycyclic aromatic hydrocarbon ubiquitous in the environment, is metabolized by the hepatic microsomal fraction of immature Sprague-Dawley rats pretreated with Aroclor 1254 to 27 ethyl acetate-extractable metabolites. More than half of these metabolites (51%) consisted of trans-1,2-; -3,4-; and -5,6-dihydrodiols including their identified secondary metabolites. The three trans-dihydrodiols were highly enriched in their R,R enantiomers as determined by high performance liquid chromatography on suitable chiral stationary phases. Determination of the bacterial mutagenicity by measuring the reversion rate of histidine-dependent Salmonella typhimurium TA100 to histidine prototrophy revealed marked differences in the mutagenicity of the enantiomers of the trans-dihydrodiols of DBA when activated by the same metabolizing system as used in the metabolism studies. In the case of trans-1,2- and -5,6-dihydrodiol, the S,S enantiomers were converted to more mutagenic metabolites than their corresponding optical antipodes, whereas in the case of trans-3,4-dihydrodiol it was the R,R enantiomer that produced the stronger mutagens. Therefore, both regio- and stereoselectivity of the metabolizing enzymes attribute to the dominant role of trans-3,4-dihydrodiol in the mutagenicity of DBA.
- OSTI ID:
- 5848625
- Journal Information:
- Environmental Health Perspectives; (USA), Journal Name: Environmental Health Perspectives; (USA) Vol. 88; ISSN 0091-6765; ISSN EVHPA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Metabolic conversion of dibenz(a,h)anthracene (+/-)trans-1,2-dihydrodiol and chrysene (+/-)trans-3,4-dihydrodiol to vicinal dihydrodiol epoxides
Stereoselective fungal metabolism of 7,12-dimethylbenz(a)anthracene: identification and enantiomeric resolution of a K-region dihydrodiol
Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
ANIMALS
AROMATICS
AZOLES
BACTERIA
BODY
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CYTOCHROME OXIDASE
DIGESTIVE SYSTEM
ENANTIOMORPHS
ENZYMES
GLANDS
HAEM DEHYDROGENASES
HETEROCYCLIC ACIDS
HETEROCYCLIC COMPOUNDS
HISTIDINE
HYDROCARBONS
IMIDAZOLES
LIVER
MAMMALS
METABOLIC ACTIVATION
METABOLISM
METABOLITES
MICROORGANISMS
MICROSOMES
MUTAGENS
MUTANTS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
POLYCYCLIC AROMATIC HYDROCARBONS
RATS
REVERTANTS
RIBOSOMES
RODENTS
SALMONELLA
SALMONELLA TYPHIMURIUM
STEREOCHEMISTRY
VERTEBRATES