A comparative investigation of DNA adducts, DNA strand breaks and gene mutations induced by benzo[a]pyrene and (±)-anti-benzo[a]pyrene-7,8-diol 9,10-oxide in cultured human cells

Hanelt, Sabine; Helbig, Rainer; Hartmann, Andreas; Lang, Mathias; Seidel, Albrecht; Speit, Günter

doi:10.1016/s0165-1218(97)00019-0

Cited by 40 publications

(30 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, under our experimental setting using alkaline condition, the BPDE-induced DNA adducts and oxidative damages can be converted into DNA strand breaks that are detectable using the alkaline comet assay [25,39,40]. Recognition and incision are the rate-limiting steps in NER while rejoining of DNA strand breaks is a rapid process with a halftime of a few minutes in most cell types [41].…”

Section: Discussionmentioning

confidence: 95%

“…Consequently, our gamma-radiation-challenged comet assay reflects the net results of DNA damage and fast repair. There have been some reports that XPC may be involved in repairing DSBs [35,39,40]. Despras et al recently reported that in XPC-proficient cells, XPC protein is released from nuclear structures after induction of DSBs and long-term XPC silencing reduces DSB repair [40].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Modulation of DNA damage/DNA repair capacity by XPC polymorphisms

et al. 2008

View full text Add to dashboard Cite

XPC, a key protein in the nucleotide excision repair (NER) pathway, recognizes damaged DNA and initiates NER. Genetic variations in the XPC gene might be associated with altered DNA repair capacities (DRC). In this study, we genotyped three XPC polymorphisms, Ala499Val (C→T), PAT (-/+) and Lys939Gln (A→C), and measured the DNA damage/DRC by alkaline comet assay challenged by BPDE and gamma-radiation in 476 healthy subjects. We also evaluated the associations between DNA damage/DRC and genotypes of XPC polymorphisms. Compared with the XPC Lys939Gln homozygous wild type (AA) subjects, subjects with the variant alleles (AC and CC) had significantly higher DNA damages induced by BPDE (Median and 95% confidence interval [CI]: 3.16 (3.01-3.44) vs. 2.88 (2.51-3.05), P=0.01), and gamma-radiation (4.18(3.94-4.44) vs. 3.71 (3.49-4.04), P=0.01). However, subjects with the variant alleles (CT and TT) of Ala499Val exhibited a 8.6 % and 13.1% decrease in DNA damages induced by BPDE (P=0.05) and gamma-radiation (P=0.001), respectively. Significant correlations were found between genotypes and induced DNA damages in XPC Lys939Gln (For BPDE: R=0.12, P=0.01; for gamma-radiation: R=0.094, P=0.046) and Ala499Val (For BPDE: R=-0.11, P=0.03; for gamma-radiation: R=-0.16, P=0.0009). The haplotypes "T-A" (in the order of Ala499Val-PAT-Lys939Gln) was associated with the lowest DNA damages. Our results suggested that the DRC of host cells might be modulated by specific XPC polymorphisms.

show abstract

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Modulation of DNA damage/DNA repair capacity by XPC polymorphisms

et al. 2008

View full text Add to dashboard Cite

show abstract

“…This anti-benzo [a]pyrene -7,8-diol-9,10-oxide-deoxyguanosine adduct has been detected in incubations of benzo [a]pyrene with calf thymus DNA or with Chinese hamster lung V79 cells or V79 cell nuclei in the presence of an Aroclor 1254-induced rat liver preparation (Sebti & Baird, 1984;Bodell et al, 1989), in mouse, rat and hamster embryo cells exposed to benzo [a]pyrene in culture (Sebti et al, 1985), in mouse skin DNA after topical treatment with benzo [a]pyrene (Ashurst et al, 1983;Bodell et al, 1989;Chen et al, 1996), in epidermal and dermal skin of mice treated topically with benzo [a]pyrene (Huckle et al, 1986), in mouse lung and liver after treatment with benzo [a]pyrene by gavage (Kulkarni & Anderson, 1984), in rat liver, lung and peripheral blood lymphocytes after intraperitoneal treatment with benzo [a]pyrene (Garner et al, 1985;Ross et al, 1990), in mouse skin explant cultures exposed to benzo [a]pyrene (Huckle et al, 1986), in human bronchus and peripheral lung explants exposed to benzo [a]pyrene (Shinohara & Cerutti, 1977;Garner et al, 1985), in human mammary epithelial cells exposed to benzo [a]pyrene (Moore et al, 1987), in human MRC5CV1 fibroblast cells exposed to benzo [a]pyrene in the presence of an Aroclor 1254-induced rat liver fraction (Hanelt et al, 1997) and in human epithelial lung BEAS-2B cells exposed to benzo [a]pyrene without an activation system (van Agen et al, 1997).…”

Section: (I)mentioning

confidence: 99%

“…Benzo [a]pyrene induced DNA strand breaks and hypoxanthine(guanine)phosphoribosyltransferase (HPRT) gene mutation (6-thioguanine resistance) in human MRC5CV1 fibroblast cells in the presence of an Aroclor 1254-induced rat liver fraction (Hanelt et al, 1997). It induced micronuclei and anchorage-independent growth (cell transformation) in human epithelial lung BEAS-2B cells (van Agen et al, 1997).…”

Section: (I)mentioning

confidence: 99%

“…An antibenzo [a]pyrene-7,8-diol-9,10-oxide-deoxyguanosine adduct was detected in Chinese hamster V79 cells , in mouse skin DNA after topical treatment with anti-benzo [a]pyrene -7,8-diol-9,10-oxide (Chen et al, 1996), in human A549 epithelial lung carcinoma cells (Dreij et al, 2005), in human lymphoblasts in vitro (Vähäkangas et al, 1985) and in human fibroblasts (Hanelt et al, 1997).…”

Section: (V) Evidence For the Diol Epoxide Pathway As A Mechanism Of mentioning

confidence: 99%

See 1 more Smart Citation

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

Analysis of mutagens with single cell gel electrophoresis, flow cytometry, and forward mutation assays in an isolated clone of Chinese hamster ovary cells

Wagner

Rayburn

Anderson

et al. 1998

Environ. Mol. Mutagen.

View full text Add to dashboard Cite

We investigated the induction of DNA strand breaks in the single cell gel electrophoresis (SCGE or comet) assay with whole cell clastogenicity measured with flow cytometric analysis in cells from an isolated clone of the Chinese hamster ovary (CHO) AS52 cell line. Under identical treatment conditions the responses were compared with forward mutation at gpt using 2‐acetoxyacetylaminofluorene (2AAAF), ultraviolet radiation (UV) and ethyl methanesulfonate (EMS). Cytotoxicity for each agent was evaluated in the SCGE and forward mutation assays. Forward mutation was 4–10‐fold more sensitive than DNA strand breaks detected in the SCGE assay. For 2AAAF and EMS, the kinetics of the induction of genetic damage were similar for the three assays, although there were differences in sensitivity. With UV, the induction kinetics of gpt mutation differed from that expressed by SCGE and flow cytometric analysis. With the chemical mutagens 2AAAF and EMS, there was a high correlation between the SCGE assay and forward mutation and also between the SCGE assay and flow cytometry. There was no significant correlation between flow cytometry and forward mutation. With UV, only the SCGE assay and flow cytometry were correlated. Agent‐specific variations in the intragenomic distribution of DNA damage for each mutagen was measured in the SCGE assay. Environ. Mol. Mutagen. 32:360–368, 1998 © 1998 Wiley‐Liss, Inc.

show abstract

A comparative investigation of DNA adducts, DNA strand breaks and gene mutations induced by benzo[a]pyrene and (±)-anti-benzo[a]pyrene-7,8-diol 9,10-oxide in cultured human cells

Cited by 40 publications

References 48 publications

Modulation of DNA damage/DNA repair capacity by XPC polymorphisms

Modulation of DNA damage/DNA repair capacity by XPC polymorphisms

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

Analysis of mutagens with single cell gel electrophoresis, flow cytometry, and forward mutation assays in an isolated clone of Chinese hamster ovary cells

Contact Info

Product

Resources

About