Formation benzo pyrene

Fig. 10.13. Metabolism of benzo[ ]pyrene (10.34). Shown are stereoselective formation of three isomeric epoxides, EH-catalyzed, stereoselective hydration to the dihydrodiols 10.35, 10.36, and 10.37, and, finally, 9,10-epoxidation of 10.36 to the bay-region diol epoxide 10.38. The latter exists as...

Daniel FB, Schut HAJ, Sandwisch DW, et al Interspecies comparisons of benzo[ ]pyrene metabolism and DNA-adduct formation in cultmed human and animal bladder and tracheobronchial tissues. Cancer Res MAI 2M 4729, 1983... 

At low temperatures, in situations where there is relatively little 02, pyrolysis reactions (i.e. reactions where decomposition takes place as a result of heat) may cause a rearrangement of atoms that can lead to the formation of polycyclic aromatic hydrocarbons (see Section 2.7) during combustion. The most notorious of these is benzo[ ]pyrene (B[ ]P see Fig. 2.4), a cancer-inducing compound. 

Stable Isotopes other than deuterium have also been used in some novel approaches for studying reactive metabolite formation. Benzo[a]pyrene, another potent polycyclic hydrocarbon carcinogen, was incubated with cofactors and rat liver mlcrosomes in an atmosphere of g Oj to investigate whether or not 6-oxybenzo[a]pyrene radical was formed. Electron spin... 

Benzo[a]pyrene-3,6-quinol and other quinols are involved in toxic quinone/quinol redox cycles (Lo-RENTZEN and Ts o 1977, Loeentzen etal. 1979). Quinols are formed from the corresponding qui-nones by several reductases. They are rapidly auto-xidizes while superoxide anions are formed. Benzo[fl]pyrene-3,6-quinone has been shown to be mutagenic in the Ames test, using tester strain TA 104 (Chesis et al. 1984) or TA 102, strains which are particularly sensitive to reactive oxygen species. In male Sprague-Dawley rats, a rapid increase of unmetabolised benzo[fl]pyrene was observed in sera 3h after benzo [a] pyrene treatment followed by a sharp decrease (Kim et al. 2000). The time-dependent pattern of serum lipid peroxidation and the level of erythrocyte antioxidant enzymes were shown to be related to the concentrations of the formation of benzo[ ]pyrene-quinones, oxidatively altered lipids and antioxidant enzymes in the blood. 

The pollutant (xenobiotic) forms a stable covalent bond with its target. Examples include the phosphorylation of cholinesterases by the oxon forms of OPs, the formation of DNA adducts by the reactive epoxides of benzo[a] pyrene and other PAHs, and the binding of organomercury compounds to... 

Egaas E, U Varanasi (1982) Effects of polychlorinated biphenyls and environmental temperature on in vitro formation of benzo[a]pyrene metabolites by liver of trout (Salmo gairdneri). Biochem Pharmacol 31 561-566. 

Cerniglia CE, DT Gibson (1980a) Fungal oxidation of benzo[a]pyrene and (+/-)-fra s-7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene evidence for the formation of a benzo[a]pyrene 7,8-diol-9,10-epoxide. J Biol Chem 255 5159-5163. 

Cerniglia CE, DT Gibson (1980b) Fungal oxidation of (-l-/-)-9,10-dihydroxy-9-10-dihydrobenzo[a]pyrene formation of diastereomeric benzo[a]pyrene 9,10-diol-7,8-epoxides. Proc Natl Acad USA 77 4554-4558. 

It is worth drawing attention to the significance of other issues. In natural ecosystans, other microorganisms including bacteria are almost always present and it has been shown that, in experiments using [7,10- C]benzo[a]pyrene, incubation for 215 d mth Bjerkandera sp. strain BOS55 alone resulted in the formation of 13.5% C02 and 61% of labeled metabolites in the... 

Each plant tissue tends to have an obviously distinctive profile of flavonoids. The flavonoid content can reach about 0.5% in pollen, 10% in propolis, and about 6 mg/kg in honey. Havonoid aglycones appear to be present only in propolis and honey, while pollen contains flavanols in herosidic forms. The flavonoids in honey and propolis have been identified as flavanones and flavanones/flavanols (Campos et ah, 1990). The antimi-crobially active flavanone pinocembrine was foimd to be a major flavonoid in honey (Bogdanov, 1989). Amiot et ah (1989) studied two blossom and two honeydew Swiss honey samples and foimd that pinocembrine was the main flavonoid. Pinocembrine concentration varied between 2 and 3 mg/kg (Bogdanov, 1989). Berahia et ah (1993) analyzed sunflower honey samples and detected six flavone/flavols, four flavanone/ flavols, and pinocembrin, of which pinocembrin is the main flavonoid. The flavonoids in sunflower honey and propolis were characterized and assessed for their effects on hepatic drug-metabolizing enzymes and benzo [fl]pyrene-DNA adduct formation (Sabatier et ah, 1992 Siess et ah, 1996). 

A theoretical analysis is presented for the binding of the four dia-stereoisomers of benzo[a]pyrene diol epoxides (BPDEs) to N2(g), N6(a), 06(G) and NU(c). Molecular models for binding and stereoselectivity involving intercalation, intercalative covalently and externally bound forms are presented. Molecular mechanics calculations provide the energetics which suggest possible structures for the formation of each of the principal DNA-BPDE complexes. Stereographic projections are used to illustrate the molecular structures and steric fits. The results of previous calculations on intercalation and adduct formation of BPDE l(+) in kinked DNA (37) are summarized and extended to include the four diastereoisomers l( ) and II( ). The theoretical model is consistent with the observed experimental data. 

The results of a crystal structure formed by a trans opening of the BPDE l(+) to yield 7,8,9,10-tetrahydroxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPTOH) shows a Cde (90) conformation of the ring. The 07-HOT and O8-H8 groups are de, and the 09-H9 and 010-H10 are also de. The torsion angles of the benzo ring are in best agreement with our second most stable structure, Cde, of the anti BDE-N2(G) trans adduct as is seen from Table III. In adduct formation to N2(G) the trans adduct is the major product (13-22) ... 

McElroy, A.E., J.M. Cahill, J.D. Sisson, and K.M. Kleinow. 1991. Relative bioavailability and DNA adduct formation of benzo[a]pyrene and metabolites in the diet of the winter flounder. Comp. Biochem. Physiol. 100C 29-32. 

Warshawsky, D., T. Cody, M. Radike, B.A. Smiddy, and B. Nagel. 1983. Toxicity and metabolism of benzo[a]pyrene in the green alga Selenastrum capricomutum. Pages 1235-1245 in M. Cooke and A.J. Dennis.(eds.). Polynuclear Aromatic Hydrocarbons Formation, Metabolism and Measurement. Battelle Press, Columbus, OH. 

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