Characterization of DNA Adducts Formed by anti-Benzo[g]chrysene 11,12-Dihydrodiol 13,14-Epoxide

Szeliga, Jan; Page, John E.; Hilton, Bruce D.; Kiselyov, Alexander S.; Harvey, Ronald G.; Dunayevskiy, Yuriy M.; Vouros, Paul; Dipple, Anthony

doi:10.1021/tx00050a004

Cited by 42 publications

(38 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Fraction 3 was subjected to a further HPLC separation that resulted in fractions 3A and 3B (insert, To determine the stereochemical characteristics of the modified bases in these four oligonucleotides, the double stranded forms used in the UV melting studies (see below) were digested to the nucleotide levels using a combination of DNAse I, Nuclease P1, and SVPD. The HPLC elution times and CD spectra of these mononucleotide adducts were then compared to those of anti-DB-[a,l]PDE-N 6 -dAMP adduct standards using approaches described in the literature (12,17).…”

Section: Synthesis and Identification Of Oligonucleotides Modified Bymentioning

confidence: 99%

“…While the bay region PAH diol epoxides, e.g., (+)-and (-)-anti-BPDE, 1 bind predominantly to deoxyguanosine (14), the sterically hindered fjord region dihydrodiol epoxides of benzo[c]phenanthrene (B[c]Ph) (15,16), benzo[g]chrysene (B[g]C) (16)(17)(18), and dibenzo[a,l]pyrene (DB[a,l]P) (10,(19)(20)(21)(22) bind more extensively to deoxyadenosine than to guanine residues in native DNA to form stable adducts. These differences in reactivities have been recently discussed by Szeliga and Dipple (13).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and Characterization of Site-Specific and Stereoisomeric Fjord Dibenzo[a,l]pyrene Diol Epoxide−N⁶-Adenine Adducts: Unusual Thermal Stabilization of Modified DNA Duplexes

Ruan

Kolbanovskiy

Zhuang

et al. 2002

Chem. Res. Toxicol.

View full text Add to dashboard Cite

The fjord polycyclic aromatic hydrocarbon compound dibenzo[a,l]pyrene (DB[a,l]P) is significantly more tumorigenic than the bay region benzo[a]pyrene in animal model systems. The molecular origins of the unusually strong genotoxic properties of DB[a,l]P and its fjord region diol epoxide metabolites are of great interest and are believed to be related to the structural characteristics of the DNA adducts formed. Site-specifically modified oligonucleotides were prepared by reacting the single adenine residue in 5'-d(CTCTCACTTCC) (I) with the racemic fjord diol epoxide r11,t12-dihydrodiol-t13,14-epoxide-11,12,13,14-tetrahydrodibenzo[a,l]pyrene (anti-DB[a,l]PDE) in aqueous solutions. Four different oligonucleotides I with the single adenosine residues involving a covalent bond between the C14 position of DB[a,l]PDE and N(6)-dA are identified and purified. The CD spectra of the mononucleotide adducts are similar to those of Li et al. [Li et al. (1999) Chem. Res. Toxicol. 12, 758] who characterized DB[a,l]PDE-N(6)-dA adducts by a combination of CD and NMR methods. The stereochemical properties of each of the four DB[a,l]PDE-modified oligonucleotides were assigned on the basis of a combination of empirical CD rules and other approaches and differ from those of Li et al. The thermal melting points, T(m), of the unmodified duplex of I with its complementary strand (IC), T(m) = 43.8 +/- 0.5 degrees C, were compared with the same duplexes containing stereoisomeric anti-DB[a,l]PDE-N(6)-dA lesions. The T(m) of duplexes I.IC containing lesions with R absolute configurations at C14 of the DB[a,l]PDE residues are greater by 6-8 degrees C, while those with S configuration are lower by 6-10 degrees C. Similar effects are observed with adducts in the same sequence context derived from the fjord PAH anti-diol epoxides of benzo[g]chrysene, while duplexes containing lesions derived from benzo[c]phenanthrene diol epoxides with 1R and 1S configurations exhibit unchanged T(m) values. In contrast, the T(m) values of duplexes with lesions derived from the bay region benzo[a]pyrene diol epoxides (B[a]PDE) in the same sequence are lower by 12 degrees (10R adducts) and by 19 degrees (10S adducts). The greater thermal stabilities of duplexes with fjord PAH-N(6)-dA lesions relative to those with bay region B[a]PDE-N(6)-dA adducts, are correlated with lower susceptibilities of excision by human nucleotide excision repair enzymes [Buterin et al. (2000) Cancer Res. 60, 1849]. The implications of these relationships are discussed in terms of present knowledge of the conformations of fjord and bay region PAH diol epoxide-N(6)-dA lesions in double stranded DNA.

show abstract

Section: Synthesis and Identification Of Oligonucleotides Modified Bymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of Site-Specific and Stereoisomeric Fjord Dibenzo[a,l]pyrene Diol Epoxide−N⁶-Adenine Adducts: Unusual Thermal Stabilization of Modified DNA Duplexes

Ruan

Kolbanovskiy

Zhuang

et al. 2002

Chem. Res. Toxicol.

View full text Add to dashboard Cite

show abstract

“…The reactive metabolite of a tobacco smoke carcinogen used in this study, anti-benzo[a]pyrene dihydrodiol epoxide (BaPDE), is a planar hydrocarbon and reacts predominantly with the N 2 position of guanine residues and to smaller extent with the N 6 position of adenine residues in the DNA molecule [8]. Benzo[g]chrysene dihydrodiol epoxide (BgCDE), a potent mammary carcinogen in rats, is nonplanar in conformation and reacts extensively with the N 6 position of adenine and also with the N 2 position of guanine residues in the DNA molecule [9].…”

Section: Introductionmentioning

confidence: 99%

Protease inhibitor–induced stabilization of p21^waf1/cip1 and cell‐cycle arrest in chemical carcinogen–exposed mammary and lung cells†

Khan

Dipple

Anderson

2002

Molecular Carcinogenesis

Self Cite

View full text Add to dashboard Cite

In previous studies, we have shown that human breast and lung carcinoma cells and mouse nontransformed type II lung cells fail to undergo cell-cycle arrest in G(1) phase in response to treatment with hydrocarbon carcinogens but rather accumulate in the S phase with damaged DNA. This situation may lead to replication of DNA on a damaged template and enhance frequency of mutations. The mechanism of this G(1) arrest failure was examined. Western immunoblot analyses of MCF7 human mammary cancer cells exposed to actinomycin D (used as a positive control for G(1) cell-cycle arrest) or hydrocarbon carcinogens revealed that while all of these chemicals caused an increase in p53, only trace levels of p21(waf1/cip1) protein were observed in the hydrocarbon carcinogen-treated samples. Similarly, in murine lung E10 type II cells, p53 but not p21(waf1/cip1) protein increased in response to benzo[a]pyrene dihydrodiol epoxide. Treatment of either MCF7 mammary or E10 lung cells with the protease inhibitor calpain I resulted in increased levels of p21(waf1/cip1) protein and enhancement of arrest of the cells in early phases of the cell cycle (G(1) and early S phase). The results suggest that failure of cell-cycle arrest in carcinogen-treated mammary and lung cells is related to increased protease-mediated degradation of p21(waf1/cip1) and/or related regulatory proteins.

show abstract

“…The major adduct formed between calf thymus DNA and racemic anti-benzo [g]chrysene-11,12-diol-13,14- (Szeliga et al, 1995). Several major adducts were formed with calf thymus DNA and racemic syn-benzo [g]chrysene -11,12-diol-13,14-oxide, a trans-syn-benzo[g]chrysene-11S,12R-diol-13S,14R-oxide-deoxyadenosine adduct and a possible mixture of a trans-synbenzo [g]chrysene-11R,12S-diol-13R,14S-oxide-deoxyguanosine and trans-syn-benzo [g]chrysene-11S,12R-diol-13S,14R-oxide-deoxyguanosine (Szeliga et al, 1994).…”

Section: Dna Adducts Of Benzo[g]chrysene-1112-diol-1314-oxidesmentioning

confidence: 99%

“…Racemic anti-benzo [g]chrysene -11,12-diol-13,14-oxide was mutagenic in the shuttle vector pSP189 with 39% of the mutations at AT pairs which suggested a relationship between adduct formation at deoxyadenosine and mutation (Szeliga et al, 1995). Racemic syn-benzo [g]chrysene -11,12-diol-13,14-oxide was mutagenic in the shuttle vector pSP189 system giving A→T and G→T mutations (Szeliga et al, 1994) and in the dihydrofolate reductase gene in Chinese hamster ovary hemizygous UA21 cells giving A→T transversion base substitution in 59% of the total induced changes (Yuan et al, 1995).…”

Section: Genotoxicity Of Benzo[g]chrysene-1112-diol-1314-oxidesmentioning

confidence: 99%

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

Hellou¹,

Beach²,

Leonard³

et al. 2012

Polycyclic Aromatic Compounds

View full text Add to dashboard Cite

initiated a programme on the evaluation of the carcinogenic risk of chemicals to humans involving the production of critically evaluated monographs on individual chemicals. The programme was subsequently expanded to include evaluations of carcinogenic risks associated with exposures to complex mixtures, life-style factors and biological and physical agents, as well as those in specific occupations. The objective of the programme is to elaborate and publish in the form of monographs critical reviews of data on carcinogenicity for agents to which humans are known to be exposed and on specific exposure situations; to evaluate these data in terms of human risk with the help of international working groups of experts in chemical carcinogenesis Publications of the World Health Organization enjoy copyright protection in accordance with the provisions of Protocol 2 of the Universal Copyright Convention. All rights reserved.The International Agency for Research on Cancer welcomes requests for permission to reproduce or translate its publications, in part or in full. Requests for permission to reproduce or translate IARC publications -whether for sale or for noncommercial distribution -should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; email: permissions@who.int).The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the World Health Organization concerning the legal status of any country, territory, city, or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.The mention of specific companies or of certain manufacturers' products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters.The IARC Monographs Working Group alone is responsible for the views expressed in this publication. IARC Library Cataloguing in Publication Data NOTE TO THE READERThe term 'carcinogenic risk' in the IARC Monographs series is taken to mean that an agent is capable of causing cancer under some circumstances. The Monographs evaluate cancer hazards, despite the historical presence of the word 'risks' in the title.Inclusion of an agent in the Monographs does not imply that it is a carcinogen, only that the published data have been examined. Equally, the fact that an agent has not yet been evaluated in a Monograph does not mean that it is not carcinogenic.The evaluations of carcinogenic risk are made by international working groups of independent scientists and are qualitative in nature. No recommendation is given for regulation or legislation.Anyone who is aware of published data that may alter the evaluation of the carcinogenic risk of an agent to humans is encouraged to make this information available to the Section of IARC Monographs, International Agency for...

show abstract

Characterization of DNA Adducts Formed by anti-Benzo[g]chrysene 11,12-Dihydrodiol 13,14-Epoxide

Cited by 42 publications

References 18 publications

Synthesis and Characterization of Site-Specific and Stereoisomeric Fjord Dibenzo[a,l]pyrene Diol Epoxide−N⁶-Adenine Adducts: Unusual Thermal Stabilization of Modified DNA Duplexes

Synthesis and Characterization of Site-Specific and Stereoisomeric Fjord Dibenzo[a,l]pyrene Diol Epoxide−N⁶-Adenine Adducts: Unusual Thermal Stabilization of Modified DNA Duplexes

Protease inhibitor–induced stabilization of p21^waf1/cip1 and cell‐cycle arrest in chemical carcinogen–exposed mammary and lung cells†

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

Contact Info

Product

Resources

About

Characterization of DNA Adducts Formed by anti-Benzo[g]chrysene 11,12-Dihydrodiol 13,14-Epoxide

Cited by 42 publications

References 18 publications

Synthesis and Characterization of Site-Specific and Stereoisomeric Fjord Dibenzo[a,l]pyrene Diol Epoxide−N6-Adenine Adducts: Unusual Thermal Stabilization of Modified DNA Duplexes

Synthesis and Characterization of Site-Specific and Stereoisomeric Fjord Dibenzo[a,l]pyrene Diol Epoxide−N6-Adenine Adducts: Unusual Thermal Stabilization of Modified DNA Duplexes

Protease inhibitor–induced stabilization of p21waf1/cip1 and cell‐cycle arrest in chemical carcinogen–exposed mammary and lung cells†

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

Contact Info

Product

Resources

About

Synthesis and Characterization of Site-Specific and Stereoisomeric Fjord Dibenzo[a,l]pyrene Diol Epoxide−N⁶-Adenine Adducts: Unusual Thermal Stabilization of Modified DNA Duplexes

Synthesis and Characterization of Site-Specific and Stereoisomeric Fjord Dibenzo[a,l]pyrene Diol Epoxide−N⁶-Adenine Adducts: Unusual Thermal Stabilization of Modified DNA Duplexes

Protease inhibitor–induced stabilization of p21^waf1/cip1 and cell‐cycle arrest in chemical carcinogen–exposed mammary and lung cells†