The DOI matches its Crossref record; 23 of the 24 references it cites were found in a registry or an index.
Preferential Formation of Benzo[ a ]pyrene Adducts at Lung Cancer Mutational Hotspots in P53
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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“A chemical (benzo[ a ]pyrene) found in cigarette smoke induces genetic mutation at specific regions of the gene's DNA that is identical to the damage evident in lung cancer cells.”
From Mediators and Mechanisms of Change in Psychotherapy Research (2007) · cites this paper as Denissenko et al. 1996
Citations
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Cancer is a preventable disease that requires major lifestyle changes
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Metadata
- 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.
- Venue
- Science
- Published
- 1996-10-18
- Volume
- 274
- Issue
- 5286
- Pages
- 430-432
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- 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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