Disease relevance of Bay Region (Chemistry)

• The effects of bay-region methyl substitution on 6-nitrochrysene mutagenicity in Salmonella typhimurium and tumorigenicity in newborn mice [1].
• This study was designed to evaluate the point mutations in the murine c-Ha-ras gene of skin papillomas induced by initiation with dibenz[a,j]anthracene (DB[a,j]A), its bay-region anti-diol epoxide ((+/-)anti-DB[a,j]A-DE), and a 7,14-dimethyl analogue (7,14-diMeDB[a,j]A) [2].
• The molecular distortion in the Pbca polymorph is also larger than that in the Pnaa polymorph; this distortion is evidenced by torsion angles (13-20 degrees) in the bay region and by an out-of-plane displacement (0.8 A) of the C atom of the methylene portion of the ethyl group [the C atom attached to C(11)] [3].

High impact information on Bay Region (Chemistry)

• We report here that DNA adducts formed from benzo[a]pyrene bay-region diol epoxides can markedly affect top1 activity [4].
• The tumorigenicity results reported here are the first direct demonstration that conformation of the hydroxyl groups in a bay-region diol epoxide, in addition to the documented effect of absolute configuration, is an important determinant in the tumorigenic activity of these ultimate carcinogens [5].
• Collectively, these results indicate that the adenine adducts induced by both bay-region diol epoxides of DMBA lead to the mutation at codon 61 of H-ras and, consequently, initiate tumorigenesis in mouse skin [6].
• Major metabolites of 6-MeC were 6-MeC-1,2-diol, bay region dihydrodiols, phenols, and 6-(hydroxymethyl)chrysene [7].
• Tannic acid inhibits the mutagenicity of several polycyclic aromatic hydrocarbons (PAHs) and their bay-region diol-epoxides [8].

Chemical compound and disease context of Bay Region (Chemistry)

• Mutagenicity in Salmonella and sister chromatid exchange in mice for the bay-region syn- and anti-diol epoxides of 1,4-dimethylphenanthrene [9].
• A series of methylene-bridged and keto-bridged bay region derivatives of chrysene and phenanthrene were prepared and evaluated for mutagenic activity in Salmonella typhimurium TA100 and for tumor-initiating activity on CD-1 mouse skin [10].

Biological context of Bay Region (Chemistry)

• These results suggest that methylation of BA at C-7 greatly enhances the oxidation of the 3S,4S-dihydrodiol, while the presence of a bay-region methyl group at C-12 completely blocks the oxidation of the 3R,4R-stereoisomer [11].
• The results show that both major adducts have chromatographic properties identical to those of adducts formed when r-1,t-2-dihydroxy-t-3,4-oxy-1,2,3,4-tetrahydrochrysene reacts with DNA and provide evidence that metabolic activation of chrysene occurs via the formation of this 'bay-region' diol-epoxide [12].
• Several groups used the UvrABC endonuclease incision assay to demonstrate that methylated CG dinucleotides of the p53 gene are the preferred binding sites for the diol epoxides of bay region polycyclic aromatic hydrocarbons (PAH) [13].
• The 3'-monophosphates of the major deoxyribonucleoside adducts of five representative polynuclear aromatic hydrocarbons (PAH)-benzo[a]pyrene, benz[a]anthracene, chrysene, 5-methylchrysene and 6-methylchrysene--were prepared by reaction with DNA of the appropriate bay-region diol epoxides followed by enzymatic hydrolysis and HPLC purification [14].
• Three different modes of cytotoxicity were observed: (1) NPQ (no bay region) and DMBAQ (methylated bay region) were as cytotoxic as menadione in reducing cell survival but had less effect on cell viability [15].

Anatomical context of Bay Region (Chemistry)

• Substitution with fluorine at C-6 caused an almost 2.5-fold increase in the percentages of the putative proximate carcinogens, i.e. benzo-ring dihydrodiols with bay-region double bonds, when liver microsomes from 3-methylcholanthrene-treated rats were used [16].
• Aroclor 1254-induced microsomes were the most effective metabolisers of this compound, the major metabolites being oxidation products of the bay region A ring [17].

Associations of Bay Region (Chemistry) with chemical compounds

• The results of this study show that the high tumorigenicity of 5-MeC compared to 6-MeC is due to the remarkable tumorigenic activity of 5-MeC-1R,2S-diol-3S,4R-epoxide which, in contrast to 6-MeC-1R,2S-diol-3S,4R-epoxide, has a methyl group in the same bay region as the epoxide ring [18].
• Evidence for bay region activation of chrysene 1,2-dihydrodiol to an ultimate carcinogen [19].
• For identification of these products, markers were prepared from 5-methylchrysene bay-region dihydrodiol epoxides [20].
• Tumorigenicity of bay-region epoxides and other derivatives of chrysene and phenanthrene in newborn mice [21].
• Among the R,S,S,R enantiomers, 5-MeC-1,2-diol-3,4-epoxide, which has a methyl group in the same bay region as the epoxide ring, was most reactive toward DNA, and in particular toward dGuo [22].

Gene context of Bay Region (Chemistry)

• With GSTM1-1, the bay-region diol epoxides, in particular the syn-diastereomers were in most cases more efficiently conjugated with GSH than the fjord-region analogues [23].
• We have determined the tumor-initiating activity of (+/-)syn- and (+/-)anti-7,12-dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide (syn- and anti-DMBADE), the two metabolically formed bay-region diol epoxides of DMBA, and we have also analyzed mutations in the H-ras gene from tumors induced by these compounds [6].
• Consistent with earlier studies of other PAH, calculations by the INDO method of the ease of carbon cation formation from a bay region diol epoxide yielded a set of values which gave a good correlation with carcinogenicity [24].
• These studies indicate that tumorigenic activity of methylated phenanthrenes requires inhibition of dihydrodiol formation at the K-region (9,10-positions) in addition to a bay-region methyl group and a free peri position, both adjacent to an unsubstituted angular ring [25].
• On the basis of this structural information, new catalysts were prepared in which the "bay region" tert-butyl groups were replaced by trimethylsilyl groups [26].

Analytical, diagnostic and therapeutic context of Bay Region (Chemistry)

• However, analysis of DMBA--DNA adducts by Servacel DHB chromatography and high-pressure liquid chromatography showed that treatment of cells with BHA, but not with BHT, resulted in a decreased contribution from the syn bay region dihydrodiol epoxide to overall binding [27].

References