Loading…
DNA Adducts of the Tobacco Carcinogens 2‑Amino‑9H‑pyrido[2,3‑b]indole and 4‑Aminobiphenyl Are Formed at Environmental Exposure Levels and Persist in Human Hepatocytes
Aromatic amines and structurally related heterocyclic aromatic amines (HAAs) are produced during the combustion of tobacco or during the high-temperature cooking of meat. Exposure to some of these chemicals may contribute to the etiology of several common types of human cancers. 2-Amino-9H-pyrido[2,...
Saved in:
Published in: | Chemical research in toxicology 2013-09, Vol.26 (9), p.1367-1377 |
---|---|
Main Authors: | , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | |
---|---|
cites | |
container_end_page | 1377 |
container_issue | 9 |
container_start_page | 1367 |
container_title | Chemical research in toxicology |
container_volume | 26 |
creator | Nauwelaërs, Gwendoline Bellamri, Medjda Fessard, Valérie Turesky, Robert J Langouët, Sophie |
description | Aromatic amines and structurally related heterocyclic aromatic amines (HAAs) are produced during the combustion of tobacco or during the high-temperature cooking of meat. Exposure to some of these chemicals may contribute to the etiology of several common types of human cancers. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is the most abundant HAA formed in mainstream tobacco smoke: it arises in amounts that are 25–100 times greater than the levels of the arylamine, 4-aminobiphenyl (4-ABP), a human carcinogen. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a prevalent HAA formed in cooked meats. AαC and MeIQx are rodent carcinogens; however, their carcinogenic potency in humans is unknown. A preliminary assessment of the carcinogenic potential of these HAAs in humans was conducted by examining the capacity of primary human hepatocytes to form DNA adducts of AαC and MeIQx, in comparison to 4-ABP, followed by the kinetics of DNA adduct removal by cellular enzyme repair systems. The principal DNA adducts formed were N-(deoxyguanosin-8-yl) (dG-C8) adducts. Comparable levels of DNA adducts were formed with AαC and 4-ABP, whereas adduct formation was ∼5-fold lower for MeIQx. dG-C8-AαC and dG-C8-4-ABP were formed at comparable levels in a concentration-dependent manner in human hepatocytes treated with procarcinogens over a 10,000-fold concentration range (1 nM–10 μM). Pretreatment of hepatocytes with furafylline, a selective inhibitor of cytochrome P450 1A2, resulted in a strong diminution of DNA adducts signifying that P450 1A2 is a major P450 isoform involved in bioactivation of these procarcinogens. The kinetics of adduct removal varied for each hepatocyte donor. Approximately half of the DNA adducts were removed within 24 h of treatment; however, the remaining lesions persisted over 5 days. The high levels of AαC present in tobacco smoke and its propensity to form persistent DNA adducts in human hepatocytes suggest that AαC can contribute to DNA damage and the risk of hepatocellular cancer in smokers. |
doi_str_mv | 10.1021/tx4002226 |
format | article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3904354</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1524396083</sourcerecordid><originalsourceid>FETCH-LOGICAL-a298t-6754ff8de4e470e02d31eb6d296318ba9991e4850e95d4e07ae3be99593194753</originalsourceid><addsrcrecordid>eNpdks9u1DAQxiMEokvhwAsgX5A4dMH_ktgXpGjZskgr4FAkJIQsJ57tukrs1HZW3Ruv0DfpM_EkGLatgMuMRv7N508zUxTPCX5NMCVv0hXHmFJaPShmpKR4XmKCHxYzLCSbUyq-HhVPYrzAmGS8flwcUSakkKSaFTfvPjaoMWbqUkR-g9IW0Jlvddd5tNChs86fg4uI_vxx3Qy5ylmuchj3wRr_jZ6wXLTfrTO-B6SdQfwObe24BbfvURMAnfowgEE6oaXb2eDdAC7pHi2vRh-nDKxhB338o_AZQrQxIevQahp0jjDq5Lt9gvi0eLTRfYRnt_m4-HK6PFus5utP7z8smvVcUynSvKpLvtkIAxx4jQFTwwi0laGyYkS0WkpJgIsSgywNB1xrYC1IWUpGJK9Ldly8PeiOU5uNd9lt0L0agx102Cuvrfr3xdmtOvc7xSTmrORZ4OQgsP2vbdWslXURwqAwFpWUuN6RjL-6_S_4ywliUoONHfS9duCnqPJeOZMVFiyjL_62di9-t9UMvDwAuovqwk_B5UkpgtXva1H318J-AftWtWQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1524396083</pqid></control><display><type>article</type><title>DNA Adducts of the Tobacco Carcinogens 2‑Amino‑9H‑pyrido[2,3‑b]indole and 4‑Aminobiphenyl Are Formed at Environmental Exposure Levels and Persist in Human Hepatocytes</title><source>American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list)</source><creator>Nauwelaërs, Gwendoline ; Bellamri, Medjda ; Fessard, Valérie ; Turesky, Robert J ; Langouët, Sophie</creator><creatorcontrib>Nauwelaërs, Gwendoline ; Bellamri, Medjda ; Fessard, Valérie ; Turesky, Robert J ; Langouët, Sophie</creatorcontrib><description>Aromatic amines and structurally related heterocyclic aromatic amines (HAAs) are produced during the combustion of tobacco or during the high-temperature cooking of meat. Exposure to some of these chemicals may contribute to the etiology of several common types of human cancers. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is the most abundant HAA formed in mainstream tobacco smoke: it arises in amounts that are 25–100 times greater than the levels of the arylamine, 4-aminobiphenyl (4-ABP), a human carcinogen. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a prevalent HAA formed in cooked meats. AαC and MeIQx are rodent carcinogens; however, their carcinogenic potency in humans is unknown. A preliminary assessment of the carcinogenic potential of these HAAs in humans was conducted by examining the capacity of primary human hepatocytes to form DNA adducts of AαC and MeIQx, in comparison to 4-ABP, followed by the kinetics of DNA adduct removal by cellular enzyme repair systems. The principal DNA adducts formed were N-(deoxyguanosin-8-yl) (dG-C8) adducts. Comparable levels of DNA adducts were formed with AαC and 4-ABP, whereas adduct formation was ∼5-fold lower for MeIQx. dG-C8-AαC and dG-C8-4-ABP were formed at comparable levels in a concentration-dependent manner in human hepatocytes treated with procarcinogens over a 10,000-fold concentration range (1 nM–10 μM). Pretreatment of hepatocytes with furafylline, a selective inhibitor of cytochrome P450 1A2, resulted in a strong diminution of DNA adducts signifying that P450 1A2 is a major P450 isoform involved in bioactivation of these procarcinogens. The kinetics of adduct removal varied for each hepatocyte donor. Approximately half of the DNA adducts were removed within 24 h of treatment; however, the remaining lesions persisted over 5 days. The high levels of AαC present in tobacco smoke and its propensity to form persistent DNA adducts in human hepatocytes suggest that AαC can contribute to DNA damage and the risk of hepatocellular cancer in smokers.</description><identifier>ISSN: 0893-228X</identifier><identifier>EISSN: 1520-5010</identifier><identifier>DOI: 10.1021/tx4002226</identifier><identifier>PMID: 23898916</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Aminobiphenyl Compounds - chemical synthesis ; Aminobiphenyl Compounds - chemistry ; Aminobiphenyl Compounds - pharmacology ; Carbolines - chemical synthesis ; Carbolines - chemistry ; Carbolines - pharmacology ; Carcinogens - chemical synthesis ; Carcinogens - chemistry ; Carcinogens - pharmacology ; Cells, Cultured ; Cytochrome P-450 CYP1A2 - metabolism ; Cytochrome P-450 CYP1A2 Inhibitors ; DNA Adducts - chemical synthesis ; DNA Adducts - chemistry ; DNA Adducts - drug effects ; Dose-Response Relationship, Drug ; Environmental Exposure - adverse effects ; Hepatocytes - cytology ; Hepatocytes - drug effects ; Hepatocytes - metabolism ; Humans ; Life Sciences ; Structure-Activity Relationship ; Toxicology</subject><ispartof>Chemical research in toxicology, 2013-09, Vol.26 (9), p.1367-1377</ispartof><rights>Copyright © 2013 American Chemical Society</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0001-9046-9117 ; 0000-0002-0016-5425</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23898916$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-00869907$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Nauwelaërs, Gwendoline</creatorcontrib><creatorcontrib>Bellamri, Medjda</creatorcontrib><creatorcontrib>Fessard, Valérie</creatorcontrib><creatorcontrib>Turesky, Robert J</creatorcontrib><creatorcontrib>Langouët, Sophie</creatorcontrib><title>DNA Adducts of the Tobacco Carcinogens 2‑Amino‑9H‑pyrido[2,3‑b]indole and 4‑Aminobiphenyl Are Formed at Environmental Exposure Levels and Persist in Human Hepatocytes</title><title>Chemical research in toxicology</title><addtitle>Chem. Res. Toxicol</addtitle><description>Aromatic amines and structurally related heterocyclic aromatic amines (HAAs) are produced during the combustion of tobacco or during the high-temperature cooking of meat. Exposure to some of these chemicals may contribute to the etiology of several common types of human cancers. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is the most abundant HAA formed in mainstream tobacco smoke: it arises in amounts that are 25–100 times greater than the levels of the arylamine, 4-aminobiphenyl (4-ABP), a human carcinogen. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a prevalent HAA formed in cooked meats. AαC and MeIQx are rodent carcinogens; however, their carcinogenic potency in humans is unknown. A preliminary assessment of the carcinogenic potential of these HAAs in humans was conducted by examining the capacity of primary human hepatocytes to form DNA adducts of AαC and MeIQx, in comparison to 4-ABP, followed by the kinetics of DNA adduct removal by cellular enzyme repair systems. The principal DNA adducts formed were N-(deoxyguanosin-8-yl) (dG-C8) adducts. Comparable levels of DNA adducts were formed with AαC and 4-ABP, whereas adduct formation was ∼5-fold lower for MeIQx. dG-C8-AαC and dG-C8-4-ABP were formed at comparable levels in a concentration-dependent manner in human hepatocytes treated with procarcinogens over a 10,000-fold concentration range (1 nM–10 μM). Pretreatment of hepatocytes with furafylline, a selective inhibitor of cytochrome P450 1A2, resulted in a strong diminution of DNA adducts signifying that P450 1A2 is a major P450 isoform involved in bioactivation of these procarcinogens. The kinetics of adduct removal varied for each hepatocyte donor. Approximately half of the DNA adducts were removed within 24 h of treatment; however, the remaining lesions persisted over 5 days. The high levels of AαC present in tobacco smoke and its propensity to form persistent DNA adducts in human hepatocytes suggest that AαC can contribute to DNA damage and the risk of hepatocellular cancer in smokers.</description><subject>Aminobiphenyl Compounds - chemical synthesis</subject><subject>Aminobiphenyl Compounds - chemistry</subject><subject>Aminobiphenyl Compounds - pharmacology</subject><subject>Carbolines - chemical synthesis</subject><subject>Carbolines - chemistry</subject><subject>Carbolines - pharmacology</subject><subject>Carcinogens - chemical synthesis</subject><subject>Carcinogens - chemistry</subject><subject>Carcinogens - pharmacology</subject><subject>Cells, Cultured</subject><subject>Cytochrome P-450 CYP1A2 - metabolism</subject><subject>Cytochrome P-450 CYP1A2 Inhibitors</subject><subject>DNA Adducts - chemical synthesis</subject><subject>DNA Adducts - chemistry</subject><subject>DNA Adducts - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Environmental Exposure - adverse effects</subject><subject>Hepatocytes - cytology</subject><subject>Hepatocytes - drug effects</subject><subject>Hepatocytes - metabolism</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Structure-Activity Relationship</subject><subject>Toxicology</subject><issn>0893-228X</issn><issn>1520-5010</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNpdks9u1DAQxiMEokvhwAsgX5A4dMH_ktgXpGjZskgr4FAkJIQsJ57tukrs1HZW3Ruv0DfpM_EkGLatgMuMRv7N508zUxTPCX5NMCVv0hXHmFJaPShmpKR4XmKCHxYzLCSbUyq-HhVPYrzAmGS8flwcUSakkKSaFTfvPjaoMWbqUkR-g9IW0Jlvddd5tNChs86fg4uI_vxx3Qy5ylmuchj3wRr_jZ6wXLTfrTO-B6SdQfwObe24BbfvURMAnfowgEE6oaXb2eDdAC7pHi2vRh-nDKxhB338o_AZQrQxIevQahp0jjDq5Lt9gvi0eLTRfYRnt_m4-HK6PFus5utP7z8smvVcUynSvKpLvtkIAxx4jQFTwwi0laGyYkS0WkpJgIsSgywNB1xrYC1IWUpGJK9Ldly8PeiOU5uNd9lt0L0agx102Cuvrfr3xdmtOvc7xSTmrORZ4OQgsP2vbdWslXURwqAwFpWUuN6RjL-6_S_4ywliUoONHfS9duCnqPJeOZMVFiyjL_62di9-t9UMvDwAuovqwk_B5UkpgtXva1H318J-AftWtWQ</recordid><startdate>20130916</startdate><enddate>20130916</enddate><creator>Nauwelaërs, Gwendoline</creator><creator>Bellamri, Medjda</creator><creator>Fessard, Valérie</creator><creator>Turesky, Robert J</creator><creator>Langouët, Sophie</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7T2</scope><scope>7TM</scope><scope>7U1</scope><scope>7U2</scope><scope>7U7</scope><scope>C1K</scope><scope>1XC</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-9046-9117</orcidid><orcidid>https://orcid.org/0000-0002-0016-5425</orcidid></search><sort><creationdate>20130916</creationdate><title>DNA Adducts of the Tobacco Carcinogens 2‑Amino‑9H‑pyrido[2,3‑b]indole and 4‑Aminobiphenyl Are Formed at Environmental Exposure Levels and Persist in Human Hepatocytes</title><author>Nauwelaërs, Gwendoline ; Bellamri, Medjda ; Fessard, Valérie ; Turesky, Robert J ; Langouët, Sophie</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a298t-6754ff8de4e470e02d31eb6d296318ba9991e4850e95d4e07ae3be99593194753</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Aminobiphenyl Compounds - chemical synthesis</topic><topic>Aminobiphenyl Compounds - chemistry</topic><topic>Aminobiphenyl Compounds - pharmacology</topic><topic>Carbolines - chemical synthesis</topic><topic>Carbolines - chemistry</topic><topic>Carbolines - pharmacology</topic><topic>Carcinogens - chemical synthesis</topic><topic>Carcinogens - chemistry</topic><topic>Carcinogens - pharmacology</topic><topic>Cells, Cultured</topic><topic>Cytochrome P-450 CYP1A2 - metabolism</topic><topic>Cytochrome P-450 CYP1A2 Inhibitors</topic><topic>DNA Adducts - chemical synthesis</topic><topic>DNA Adducts - chemistry</topic><topic>DNA Adducts - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Environmental Exposure - adverse effects</topic><topic>Hepatocytes - cytology</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - metabolism</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Structure-Activity Relationship</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nauwelaërs, Gwendoline</creatorcontrib><creatorcontrib>Bellamri, Medjda</creatorcontrib><creatorcontrib>Fessard, Valérie</creatorcontrib><creatorcontrib>Turesky, Robert J</creatorcontrib><creatorcontrib>Langouët, Sophie</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Nucleic Acids Abstracts</collection><collection>Risk Abstracts</collection><collection>Safety Science and Risk</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Chemical research in toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nauwelaërs, Gwendoline</au><au>Bellamri, Medjda</au><au>Fessard, Valérie</au><au>Turesky, Robert J</au><au>Langouët, Sophie</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA Adducts of the Tobacco Carcinogens 2‑Amino‑9H‑pyrido[2,3‑b]indole and 4‑Aminobiphenyl Are Formed at Environmental Exposure Levels and Persist in Human Hepatocytes</atitle><jtitle>Chemical research in toxicology</jtitle><addtitle>Chem. Res. Toxicol</addtitle><date>2013-09-16</date><risdate>2013</risdate><volume>26</volume><issue>9</issue><spage>1367</spage><epage>1377</epage><pages>1367-1377</pages><issn>0893-228X</issn><eissn>1520-5010</eissn><abstract>Aromatic amines and structurally related heterocyclic aromatic amines (HAAs) are produced during the combustion of tobacco or during the high-temperature cooking of meat. Exposure to some of these chemicals may contribute to the etiology of several common types of human cancers. 2-Amino-9H-pyrido[2,3-b]indole (AαC) is the most abundant HAA formed in mainstream tobacco smoke: it arises in amounts that are 25–100 times greater than the levels of the arylamine, 4-aminobiphenyl (4-ABP), a human carcinogen. 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a prevalent HAA formed in cooked meats. AαC and MeIQx are rodent carcinogens; however, their carcinogenic potency in humans is unknown. A preliminary assessment of the carcinogenic potential of these HAAs in humans was conducted by examining the capacity of primary human hepatocytes to form DNA adducts of AαC and MeIQx, in comparison to 4-ABP, followed by the kinetics of DNA adduct removal by cellular enzyme repair systems. The principal DNA adducts formed were N-(deoxyguanosin-8-yl) (dG-C8) adducts. Comparable levels of DNA adducts were formed with AαC and 4-ABP, whereas adduct formation was ∼5-fold lower for MeIQx. dG-C8-AαC and dG-C8-4-ABP were formed at comparable levels in a concentration-dependent manner in human hepatocytes treated with procarcinogens over a 10,000-fold concentration range (1 nM–10 μM). Pretreatment of hepatocytes with furafylline, a selective inhibitor of cytochrome P450 1A2, resulted in a strong diminution of DNA adducts signifying that P450 1A2 is a major P450 isoform involved in bioactivation of these procarcinogens. The kinetics of adduct removal varied for each hepatocyte donor. Approximately half of the DNA adducts were removed within 24 h of treatment; however, the remaining lesions persisted over 5 days. The high levels of AαC present in tobacco smoke and its propensity to form persistent DNA adducts in human hepatocytes suggest that AαC can contribute to DNA damage and the risk of hepatocellular cancer in smokers.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>23898916</pmid><doi>10.1021/tx4002226</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-9046-9117</orcidid><orcidid>https://orcid.org/0000-0002-0016-5425</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0893-228X |
ispartof | Chemical research in toxicology, 2013-09, Vol.26 (9), p.1367-1377 |
issn | 0893-228X 1520-5010 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3904354 |
source | American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list) |
subjects | Aminobiphenyl Compounds - chemical synthesis Aminobiphenyl Compounds - chemistry Aminobiphenyl Compounds - pharmacology Carbolines - chemical synthesis Carbolines - chemistry Carbolines - pharmacology Carcinogens - chemical synthesis Carcinogens - chemistry Carcinogens - pharmacology Cells, Cultured Cytochrome P-450 CYP1A2 - metabolism Cytochrome P-450 CYP1A2 Inhibitors DNA Adducts - chemical synthesis DNA Adducts - chemistry DNA Adducts - drug effects Dose-Response Relationship, Drug Environmental Exposure - adverse effects Hepatocytes - cytology Hepatocytes - drug effects Hepatocytes - metabolism Humans Life Sciences Structure-Activity Relationship Toxicology |
title | DNA Adducts of the Tobacco Carcinogens 2‑Amino‑9H‑pyrido[2,3‑b]indole and 4‑Aminobiphenyl Are Formed at Environmental Exposure Levels and Persist in Human Hepatocytes |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-02T18%3A55%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=DNA%20Adducts%20of%20the%20Tobacco%20Carcinogens%202%E2%80%91Amino%E2%80%919H%E2%80%91pyrido%5B2,3%E2%80%91b%5Dindole%20and%204%E2%80%91Aminobiphenyl%20Are%20Formed%20at%20Environmental%20Exposure%20Levels%20and%20Persist%20in%20Human%20Hepatocytes&rft.jtitle=Chemical%20research%20in%20toxicology&rft.au=Nauwelae%CC%88rs,%20Gwendoline&rft.date=2013-09-16&rft.volume=26&rft.issue=9&rft.spage=1367&rft.epage=1377&rft.pages=1367-1377&rft.issn=0893-228X&rft.eissn=1520-5010&rft_id=info:doi/10.1021/tx4002226&rft_dat=%3Cproquest_pubme%3E1524396083%3C/proquest_pubme%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-a298t-6754ff8de4e470e02d31eb6d296318ba9991e4850e95d4e07ae3be99593194753%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1524396083&rft_id=info:pmid/23898916&rfr_iscdi=true |