Cited by 1,650Carcinogens and Genotoxicity AssessmentCancer-related Molecular PathwaysDNA Repair Mechanisms

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Preferential Formation of Benzo[ a ]pyrene Adducts at Lung Cancer Mutational Hotspots in P53

Denissenko, Mikhail F., Pao, Annie, Tang, Moon-shong, Pfeifer, Gerd P.·1996·Science

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Abstract

Cigarette smoke carcinogens such as benzo[ a ]pyrene are implicated in the development of lung cancer. The distribution of benzo[ a ]pyrene diol epoxide (BPDE) adducts along exons of the P53 gene in BPDE-treated HeLa cells and bronchial epithelial cells was mapped at nucleotide resolution. Strong and selective adduct formation occurred at guanine positions in codons 157, 248, and 273. These same positions are the major mutational hotspots in human lung cancers. Thus, targeted adduct formation rather than phenotypic selection appears to shape the P53 mutational spectrum in lung cancer. These results provide a direct etiological link between a defined chemical carcinogen and human cancer.

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Authors: Denissenko, M. F., Pao, A., Tang, M.-S., & Pfeifer, G. P.
Affiliations: Beckman Research Institute (US)
A. Pao and M.-s. Tang, M. D. Anderson Cancer Center, University of Texas, Science Park, Smithville, TX 78957, USA.
ORCID: Tang, Moon-shong
Pfeifer, Gerd P.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1996-10-18
Volume: 274
Issue: 5286
Pages: 430-432
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.274.5286.430
OpenAlex: W1976056213
Cited by: 1,650
References: 24
Citations by year: 2026: 16 · 2025: 16 · 2024: 17 · 2023: 16 · 2022: 15 · 2021: 26 · 2020: 26 · 2019: 28 · 2018: 29 · 2017: 48 · 2016: 40 · 2015: 45 · 2014: 63 · 2013: 39 · 2012: 69
FWCI: 40.80
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (1r01ca065652-01a1)
National Cancer Institute (CA65652)
National Institute of Environmental Health Sciences (ES03124, R01ES003124)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords: benzo[a]pyrene, benzo[a]pyrene diol epoxide, DNA adducts, p53, lung cancer, mutational hotspots, tobacco smoke carcinogens, mutation spectrum, HeLa cells, bronchial epithelial cells, guanine adducts
MeSH terms: Bronchi, Carcinogens, Cells, Cultured, Codon, Exons, Fibroblasts, HeLa Cells, Humans, Lung Neoplasms, Mutagens, Mutation, Plants, Toxic, Smoke, Nicotiana, 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide, Dinucleoside Phosphates, Genes, p53, DNA Adducts

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Preferential Formation of Benzo[ a ]pyrene Adducts at Lung Cancer Mutational Hotspots in P53

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