Hongmee Lee

Syntheses of polycyclic aromatic hydrocarbon-nucleoslde and oligonucleotide adducts specifically alkylated on the amino functions of deoxyguanosine and deoxyadenosine

Abstract Efficient syntheses of 1-pyrenylmethyl-mononucleoside adducts with the hydrocarbon moiety attached to the exocyclic amino functions of deoxyguanosine and deoxyadenosine are described.

Spectroscopic Properties of Polycyclic Aromatic Compounds

Abstract Fluorescence emission spectra have been measured for acenaphthylene, aceanthrylene, acephenanthrylene, benz[ e ]aceanthrylene, 3-methylbenz[ j ]aceanthrylene, 6-methylbenz[ j ]aceanthrylene, benzo[ def ]cyclopenta[ hi ]chrysene, cyclopenta[ cd ]pyrene (also called acepyrylene) and acenaphth[1,2 a ]acenaphthylene in organic nonelectrolyte solvents of varying polarity. Benz[ e ]aceanthrylene was found to exhibit probe character for many of the solvents considered; however, emission intensity ratios in benzene, toluene, p -xylene and o -xylene were too small compared against nonelectrolyte solvents of similar polarity. The effect of nitromethane as selective quenching agent was also examined. Results of these measurements show that nitromethane does quench the fluorescence emission of the nine solutes studied, which is contrary to what would be expected based upon the fact that all nine solutes are nonalternant polycyclic aromatic hydrocarbons.

Syntheses of 2-Bromopyrene and 2-Hydroxypyrene

Abstract Regiospecific monobromination of 4,5,9,10-tetrahydropyrene in the 2-posiuon is accomplished in aqueous dimethylformamide. Conversion of the previously unknown 2-bromo-4,5,9,10-tetrahydropyrene to the title compounds is described.

Induction of chromosomal aberrations in rat bone marrow cells and mutations in Salmonella typhimurium by benz[a]anthracene derivatives

Benz[a]anthracene (BA) and its derivatives containing methyl and/or ethyl groups in the 7 and/or 12 positions were tested for their ability to induce chromosome aberrations (CA) in rat bone marrow cells and for their mutagenicity to Salmonella typhimurium TA100 or TA98. The incidence of aberrant cells induced by the BA derivatives, given in lipid emulsion as a single-pulse dose of 50 mg/kg body weight into the caudal vein, was in the order: DMBA greater than EMBA greater than MEBA greater than other BA derivatives = control. The alkyl groups, at least 1 methyl group, at the 7 and 12 positions of BA seemed to be necessary to induce CA, although DEBA having ethyl groups at both the 7 and 12 positions of BA did not induce CA. DMBA or EMBA induced not only gaps and breaks but also exchanges and multiple CA, while the CA induced by other BA derivatives consisted of only gaps and breaks. 7MBA and 12MBA which exhibit carcinogenic activity intermediate between that of DMBA and BA induced few CA in the present system. However, the correlation coefficient between the logarithm incidence of aberrant cells and the carcinogenicity index calculated from the data of 9 BA derivatives including both 7MBA and 12MBA was 0.792. The relative mutagenicities of the BA derivatives with TA100 in the presence of hepatic S9 from polychlorinated biphenyl (PCB)-treated rats were in the order: BA greater than 7MBA greater than DMBA greater than 12MBA greater than 7EBA greater than EMBA greater than MEBA greater than 12EBA = DEBA = control. The results with TA98 were essentially the same as those with TA100. The results with TA100 in the presence of hepatic S9 from phenobarbital (PB)-treated rats were in the order: DMBA greater than 12MBA greater than 7MBA greater than 7EBA greater than BA greater than EMBA = MEBA greater than 12EBA = DEBA = control. These findings reveal no obvious relation between the mutagenic activities of the BA derivatives with the PCB-S9 or PB-S9 activating systems and their capacities to induce CA or their reported carcinogenicities. The incidence of CA induced by the dihydrodiols implicated as the metabolic precursors of the active diol epoxide metabolites of several of these BA derivatives was also tested. BA 3,4-dihydrodiol, like BA itself, induced few CA. However, the corresponding dihydrodiols of DMBA, 12MBA and 7MBA, induced relatively high levels of CA.(ABSTRACT TRUNCATED AT 400 WORDS)

Comparison of the sites of reaction of three polycyclic aromatic hydrocarbons in the supF gene.

The distribution of hydrocarbon-DNA adducts through the supF gene in plasmid pS189 was examined using the polymerase arrest assay. For three hydrocarbon dihydrodiol epoxides, derived from 5-methylchrysene, 7-methylbenz[a]anthracene, and benzo[a]pyrene, that exhibit a preference for reaction with guanine residues in DNA, polymerase arrest spectra were similar but not identical. For each agent, guanines in different sequence contexts exhibited varying reactivities and each specific guanine did not necessarily respond to each agent in the same fashion. Thus, sequence context together with the individual dihydrodiol epoxides chemical and physical properties all play a role in determining sites and extents of reaction within a specific gene. The polymerase arrest data were not predictive of the known sites of mutation hotspots for these dihydrodiol epoxides in the supF gene indicating that further action upon the adducted DNA by repair systems is probably necessary to determine which specific chemical adducts will ultimately give rise to mutation.

Stereoselective syn epoxidation of the dihydrodiols of dibenz[a,h] anthracene and 7-methylbenz[a] anthracene

Abstract Epoxidation of the bay region dihydrodiols of the title hydrocarbons affords stereoselectively the corresponding syn diol epoxides rather than the anticipated isomeric anti diol epoxides, indicative of a dominant cis-directing effect of the benzylic vs the allylic axial hydroxyl groups.

Reinvestigation of the jutz synthesis of benzo [e] pyrene and benzo [a] pyrene derivatives from benzanthrene

Abstract Base-catalyzed reactions of benzanthrene with “vinamidinium salts” ( 2a-c ) followed by thermal electrocyclic ring closure are regiospecific affording only benzo [e] pyrene derivatives, contrary to previous claims.

The monomethyl and dimethyl derivatives of benzo[e]pyrene

Abstract Convenient syntheses of the previously unknown complete set of six isomeric monomethyl derivatives of benzo[e]pyrene, 1-, 2-, 3-, 4-, 9- and 10-methylbenzo[e]pyrene, are described. Syntheses of 1-, 2- and 3-methylbenzo[e]pyrene were accomplished through reaction of 7H-benzanthrene (or its 1-Me derivative as appropriate) with 1, 3-bis(dimethylamino)trimethinium perchlorate (or its 1-Me derivative) followed by thermal electrocyclic ring closure accompanied by elimination and aromatization. The earlier claim16 that the analogous isomeric benzo[a]pyrene derivatives are principal products of reactions of this type is disproven. Synthesis of 3,6- and 4,5-dimethylbenzo[e]pyrene are also described. The structural assignments of all mono- and dimethyl benzo[e] pyrene products are supported by high resolution 270 MHz proton NMR spectra; the chemical shifts and coupling constants of all aromatic protons are fully assigned.

DNA Adducts Formed by syn Dihydrodiol Epoxides of Polycyclic Aromatic Hydrocarbons

Abstract A brief review of the literature on syn dihydrodiol epoxide DNA adducts is presented. NMR studies indicate that bay region substituents influence the conformation of the partially saturated ring in such adducts. However, only substitutions that lead to distortion from planarity are associated with reactivity towards deoxyadenosine residues in DNA and with greater tumorigenicity. This is similar to the situation that obtains for anti dihydrodiol epoxides.

Linear dichroism studies of conformations of carcinogen-DNA adducts. Application to covalent complexes derived from the reactions of the two enantiomers of 9,10-epoxy-9,10,11,12-tetrahydrobenzo(e)pyrene with DNA

The conformations of the adducts derived from the covalent binding of the two enantiomeric forms of 9,10-epoxy-9,10,11,12-tetrahydrobenzo(e)pyrene (BePE) with native DNA were investigated by the electric linear dichroism technique. Both enantiomers give rise to two major adducts, one of which appears to be a quasi-intercalative site (I) while the other one is an external binding site (II). While the overall linear dichroism spectra are similar, in the case of the (-) enantiomer there is a greater contribution of site II adducts. These results are markedly different from the ones obtained with the two enantiomers of anti-benzo(a)pyrene-7,8-diol-9,10-epoxide (BaPDE), where the (+) enantiomer gives rise almost exclusively to site II binding, while the (-) enantiomer gives rise to both site I and site II covalent binding. The differences in the heterogeneity of binding between BePE and anti-BaPDE enantiomers may be due to the absence of hydroxyl groups in BePE which, in the case of BaPDE, are an important factor in determining the stereoselective properties of the covalent binding to double-stranded DNA.