Dibenzo pyrene 11,12-diol

Ruan, Q., Kolbanovskiy, A., Zhuang, P., Chen, J., Krzeminski,)., Amin, S., and Geacintov, N.E. (2002) Synthesis and characterization of site-specific and stereoisomeric fjord dibenzo[a,I]pyrene diol epoxide-JV6)-adenine adducts unusual thermal stabilization of modified DNA duplexes. Chem. Res. Toxicol, 15, 249-261. 

PAHs are ubiquitous environmental pollutants known to be mutagenic and carcinogenic in mammalian cells [131, 132]. PAHs require metabolic activation that results in diol epoxide formation via reactions that are catalyzed by epoxide hydrolase and the CYP450 family of enzymes [133], Diol epoxides are highly reactive, particularly toward purines in DNA, forming guanine and adenine adducts that exist as as and trans stereoisomers [134]. Transcription past adducts derived from diol epoxides of benzo[o]pyrene (benzo[a]pyrene diol expoxide (B[a]PDE)), benzo[c]phenanthrene (benzo[c]phenanthrene diol epoxide (B[c]PhDE)), and dibenzo[a,l]pyrene (dibenzo[o,l]pyrene diol epoxide (B[a,l]PDE)) has been studied. 

GSTA2-2—Cumene hydroperoxide, fatty add hydroperoxides, dibenzo(a)-pyrene diol epoxide, CDNB-moderate, DCNB-moderate, 7-chloro-4-nitro-2-oxa-1,3-diazole, ethacrynic add (low moderate), PEITC, sulforophane. 

Lagerqvist A, Hakansson D, Prochazka G, Lundin C, Dreij K, Segerback D, Jemstrom B, Tomqvist M, Seidel A, Erixon K, Jenssen D Both replieation bypass fidelity and repair efficiency influence the yield of mutations per target dose in intact mammalian cells induced by benzo[a]pyrene-diol-epoxide and dibenzo[a4]pyrene-diol-epoxide. 

Dibenzo [a, l pyrene Dibenzo [a, l pyrene-11,12-diol-13,14-epoxide... 

Methods for the synthesis of the biologically active dihydrodiol and diol epoxide metabolites of both carcinogenic and noncarcinogenic polycyclic aromatic hydrocarbons are reviewed. Four general synthetic routes to the trans-dihydrodiol precursors of the bay region anti and syn diol epoxide derivatives have been developed. Syntheses of the oxidized metabolites of the following hydrocarbons via these methods are described benzo(a)pyrene, benz(a)anthracene, benzo-(e)pyrene, dibenz(a,h)anthracene, triphenylene, phen-anthrene, anthracene, chrysene, benzo(c)phenanthrene, dibenzo(a,i)pyrene, dibenzo(a,h)pyrene, 7-methyl-benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, 3-methylcholanthrene, 5-methylchrysene, fluoranthene, benzo(b)fluoranthene, benzo(j)fluoranthene, benzo(k)-fluoranthene, and dibenzo(a,e)fluoranthene. 

These hexacyclic hydrocarbons are generally recognized as two of the most potent unsubstituted carcinogenic PAH (38). The 3,4-dihydro-diol of dibenzo(a,i)pyrene (17) and the 1,2-dihydrodiol of dibenzo-(a,h) pyrene (lg) have been synthesized from 4-oxo-l,2,3,4-tetra-hydrodibenzo(a,i)pyrene and 1-oxo-l,2,3,4-tetrahydrodibenzo(a,h)py-rene, respectively, by Method I. (69). Treatment of these dihydro-diols with m-chloroperbenzoic acid gave the corresponding anti diol epoxides (66). 

A. Luch, S. Kishiyama, A. Seidel, J. Doehmer, H. Greim, W. M. Baird, The K-Region //z/ .v-8.9-Diol Does not Significantly Contribute as an Intermediate in the Metabolic Activation of Dibenzo[a,Z]pyrene to DNA-Binding Metabolites by Human Cytochrome P450 1A1 or 1B1 , Cancer Res. 1999, 59, 4603 - 4609. 

In the laboratory of S. Kumar, the synthesis of phenolic derivatives of frans-7,8-dihydroxy -7,8-dihydrobenzo[a]pyrene, a highly tumorigenic compound, was accomplished. The frans-vicinal diol functionality was introduced by using the "dry" Prevost conditions. The alkene was subjected to a mixture of iodine and silver benzoate in dry refluxing benzene to give a good yield of the corresponding frans-7,8-dibenzoate derivative. 

MelendezColon, V.J., Smith, C.A., Seidel, A., Luch, A., Platt, K.L., and Baird, W.M. (1997) Formation of stable adducts and absence of depurinating DNA adducts in cells and DNA treated with the potent carcinogen dibenzo[a,l] pyrene or its diol-epoxides. Proc. Natl. Acad. Sci. USA, 94, 13542-13547. 

Amin, S., Desai, D., Dai, W., Harvey, R.G., and Hecht, S.S. (1995) Tumori-genicity in newborn mice of fjord region and other sterically hindered diol epoxides of benzo[g]chrysene, dibenzo[a,l]pyrene (dibenzo[de/p] chrysene), 4H -cyclopenta[de/]chrysene and fluoranthene. Carcinogenesis, 16, 2813-2817. 

Amin, S., Krzeminski, J., Rivenson, A., Kurtzke, C., Hecht, S.S., and El-Bay-oumy, K. (1995) Mammary cardno-genidty in female CD rats of fjord region diol epoxides of benzo[c] phenanthrene, benzo[g]chrysene and dibenzo[a,l]pyrene. Carcinogenesis, 16, 1971-1974. 

Dreij, K., Seidel, A., and Jemstrom, B. (2005) Differential removal of DNA adducts derived from anti-diol epoxides of dibenzo[a,l]pyrene and benzoja] pyrene in human cells. Chem. Res. Toxicol., 18, 655-664. 

Abbreviations PAH, polycyclic aromatic hydrocarbon DE, diol epoxide PAHDE, polycyclic aromatic hydrocarbon diol epoxide PAHTC, polycyclic aromatic hydrocarbon triol carbocation TC, triol carbocation BaP, benzo[a]pyrene BeP, benzo[e]pyrene BA, benz[a]anthracene DBA, dibenz[a,h]anthracene BcPh, benzo[c)phenanthrene Ch, chrysene MCh, methylchrysene MBA, 7-methyl benz[a]anthracene DMBA, 7,12-dimethyl benz[a]anthracene EBA, 7-ethyl benz[a]anthracene DB(a,l)P, dibenzo[a,l]pyrene MSCR, mechanism-based structure-carcinogenicity relationship PMO, Perturbational molecular orbital method dA, deoxyadenosine dC, deoxycytosine dG, deoxyguanosine MOS, monoxygenase enzyme system EH, epoxide hydrolase enzyme system N2(G), exocyclic nitrogen of guanine C, electrophilic centre of PAHTC K, intercalation constant CD, circular dichroism LD, linear dichroism. 

Studies carried out by Straif et al. (2005) showed that, in mice, B[a]P caused lung tumors, by the formation of diol-epoxide and skin tumors, triggered by diol-epoxide mechanisns and cations radicals. According to these same authors, few PAHs are considered carcinogens more potent than B[a]P. However, dibenzo(a,l)pyrene seems to be a carcinogenic 10 times more potent for rats than the own B[a]P (Okona-Mensah et al., 2005). Another PAH highly potent, according to Platt et al. (1990) is the dibenzo(a,h)anthracene. 

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