Stereoselective activation of dibenzo[a,l]pyrene to (—)-anti(11R, 12S, 13S, 14R)- and (+)-syn(11S, 12R, 13S, 14R)- 11, 12-diol-13, 14-epoxides which bind extensively to deoxyadenosine residues of DNA in the human mammary carcinoma cell line MCF-7

Ralston, Sherry L.; Seidel, Albrecht; Luch, Andreas; Platt, Karl L.; Baird, William M.

doi:10.1093/carcin/16.12.2899

Cited by 126 publications

(135 citation statements)

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“…As already noted, PAH-induced mutations arise from covalent adducts of their diol epoxides to either guanine as in the case of B(a)P (Sims et al, 1974) or adenine as in the cases of DMBA and DB(a,l)P (Cheng et al, 1988;Ralston et al, 1995). The formation of the bulky BPDE adduct at the N2 position of guanine results predominantly (70%) in G?T transversions which is the mutational signature of BPDE (Ruggeri et al, 1993).…”

Section: Modes Of Selectionmentioning

confidence: 90%

“…The BPDE bound mainly to guanine residues of DNA (Weinstein et al, 1976). The diol epoxides of DMBA and DB(a,l)P bind extensively to adenine residues of DNA (Cheng et al, 1988;Ralston (Burdette, 1955). Subsequent results indicated that the PAHs had to be metabolized by target tissue in order to induce tumors, and that the metabolites could be generated by TPNH-dependent microsomal systems of liver.…”

Section: Metabolism Of Pahs and Binding To Dnamentioning

confidence: 99%

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Selective clonal expansion and microenvironmental permissiveness in tobacco carcinogenesis

Rubin

2002

Oncogene

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Historically our knowledge about the direct carcinogenic activity of cigarette smoke and its constituents grew from painting experiments on the skin of mice to produce papillomas and carcinomas. The neutral fraction of cigarette smoke condensate had most of the carcinogenic activity in this test and was rich in carcinogenic polycyclic aromatic hydrocarbons (PAHs), the most abundant by far being BP. However, the concentration of BP in the condensate was only about 2% the amount of pure BP required to cause skin tumors. In other fractions there were non-carcinogenic constituents that promoted tumor formation when applied repeatedly to mouse skin that had been initiated by a single subcarcinogenic application of BP. There were also constituents of cigarette smoke that acted as cocarcinogens when applied simultaneously with repeated applications of BP. BP was effective as an initiator at lower concentrations than as a complete carcinogen, and some non-carcinogenic PAHs in the condensate were also active initiators. It was concluded from these studies that cigarette smoke condensate is primarily a tumorpromoting and co-carcinogenic agent with weak activity as a complete carcinogen. A major effect of promoters, and possibly of co-carcinogens, is a diffuse hyperplasia which includes selective expansion of clones carrying endogenous mutations and/or mutations induced by PAHs and other carcinogens such as NNK. The induced mutations as well as damaged cells would occur throughout the exposed region and, along with the hyperplasia, increase the permissiveness of the cellular microenvironment for neoplastic expression of any potential tumor cell in its midst. Since neither the promoters nor co-carcinogens in tobacco smoke are known to interact directly with DNA, their effects can be considered epigenetic processes that act upon genetically altered cells. Examples are cited from studies of experimental skin carcinogenesis, smoking-induced histopathological changes in human lung and spontaneous transformation in cell culture to illustrate the genetic and epigenetic interactions of neoplastic development in general and their significance for smoking-induced lung cancer in particular. Certain dietary modifications that appear to be effective in moderating the promotional phase of animal and human carcinogenesis are suggested for trial in managing lung cancer.

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Section: Modes Of Selectionmentioning

confidence: 90%

Section: Metabolism Of Pahs and Binding To Dnamentioning

confidence: 99%

Selective clonal expansion and microenvironmental permissiveness in tobacco carcinogenesis

Rubin

2002

Oncogene

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“…Chinese hamster V79 cells that express human recombinant CYP1A1 produced both non-polar and polar DNA adducts from (-)-dibenzo [a,l]pyrene-11R,12R-diol (Luch et al, 1998b). Of the four non-polar DNA adducts, one was identified specifically as (-)-anti-dibenzo [a,l]pyrene-11R,12S-diol-13S,14R-oxidedeoxyadenosine (Ralston et al, 1995) and the other three were all (-)-antidibenzo [a,l]pyrene-11,12-diol-13,14-oxide-DNA adducts (Luch et al, 1998b). These four non-polar adducts were also formed exclusively in V79 cells that express human CYP1B1 after exposure to (-)-dibenzo [a,l]pyrene-11R,12R-diol.…”

Section: Dna Adducts Of Dibenzo[al]pyrene-1112-diolmentioning

confidence: 99%

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

Hellou¹,

Beach²,

Leonard³

et al. 2012

Polycyclic Aromatic Compounds

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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...

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“…For example, in MCF-7 cells, DB[a,l]PDE forms predominantly Adespecific stable adducts [117]. In Chinese hamster V79 cells, anti-DB[a,l]PDE forms both G.Cspecific and A.T-specific mutations in the Hprt gene [99].…”

Section: Preneoplastic Mutations-db[al]mentioning

confidence: 99%

The role of polycyclic aromatic hydrocarbon–DNA adducts in inducing mutations in mouse skin

Chakravarti

Venugopal

Mailander

et al. 2008

Mutation Research/Genetic Toxicology and Environmental Mutagene

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Polycyclic aromatic hydrocarbons (PAH) form stable and depurinating DNA adducts in mouse skin to induce preneoplastic mutations. Some mutations transform cells, which then clonally expand to establish tumors. Strong clues about the mutagenic mechanism can be obtained if the PAH-DNA adducts can be correlated with both preneoplastic and tumor mutations. To this end, we studied mutagenesis in PAH-treated early preneoplastic skin (1 day after exposure) and in the induced papillomas in SENCAR mice. Papillomas were studied by PCR amplification of the H-ras gene and sequencing. For benzo [a]pyrene (BP), 7, anthracene (DMBA) and dibenzo [a,l]pyrene (DB[a,l]P), the codon 13 (GGC to GTC) and codon 61 (CAA to CTA) mutations in papillomas corresponded to the relative levels of Gua and Adedepurinating adducts, despite BP and BPDHD forming significant amounts of stable DNA adducts. Such a relationship was expected for DMBA and DB[a,l]P, as they formed primarily depurinating adducts. These results suggest that depurinating adducts play a major role in forming the tumorigenic mutations. To validate this correlation, preneoplastic skin mutations were studied by cloning Hras PCR products and sequencing individual clones. DMBA-and DB[a,l]P-treated skin showed primarily A.T to G.C mutations, which correlated with the high ratio of the Ade/Gua-depurinating adducts. Incubation of skin DNA with T.G-DNA glycosylase eliminated most of these A.T to G.C mutations, indicating that they existed as G.T heteroduplexes, as would be expected if they were formed by errors in the repair of abasic sites generated by the depurinating adducts. BP and its metabolites induced mainly G.C to T.A mutations in preneoplastic skin. However, PCR over unrepaired anti-BPDE-N 2 dG adducts can generate similar mutations as artifacts of the study protocol, making it difficult to establish an adduct-mutation correlation for determining which BP-DNA adducts induce the early preneoplastic mutations. In conclusion, this study suggests that depurinating adducts play a major role in PAH mutagenesis.

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Stereoselective activation of dibenzo[a,l]pyrene to (—)-anti(11R, 12S, 13S, 14R)- and (+)-syn(11S, 12R, 13S, 14R)- 11, 12-diol-13, 14-epoxides which bind extensively to deoxyadenosine residues of DNA in the human mammary carcinoma cell line MCF-7

Cited by 126 publications

References 0 publications

Selective clonal expansion and microenvironmental permissiveness in tobacco carcinogenesis

Selective clonal expansion and microenvironmental permissiveness in tobacco carcinogenesis

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

The role of polycyclic aromatic hydrocarbon–DNA adducts in inducing mutations in mouse skin

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