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Cited by 253

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Molecular mechanisms of pulmonary carcinogenesis by polycyclic aromatic hydrocarbons (PAHs): Implications for human lung cancer

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Stading, Rachel, Gastelum, Grady, Chu, Chun, Jiang, Weiwu, Moorthy, Bhagavatula·2021·Seminars in Cancer Biology
DOI 10.1016/j.semcancer.2021.07.001
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Abstract

Lung cancer has the second highest incidence and highest mortality compared to all other cancers. Polycyclic aromatic hydrocarbon (PAH) molecules belong to a class of compounds that are present in tobacco smoke, diesel exhausts, smoked foods, as well as particulate matter (PM). PAH-derived reactive metabolites are significant contributors to lung cancer development. The formation of these reactive metabolites entails metabolism of the parent PAHs by cytochrome P4501A1/1B1 (CYP1A1/1B1) and epoxide hydrolase enzymes. These reactive metabolites then react with DNA to form DNA adducts, which contribute to key gene mutations, such as the tumor suppressor gene, p53 and are linked to pulmonary carcinogenesis. PAH exposure also leads to upregulation of CYP1A1 transcription by binding to the aryl hydrocarbon receptor (AHR) and eliciting transcription of the CYP1A1 promoter, which comprises specific xenobiotic-responsive element (XREs). While hepatic and pulmonary CYP1A1/1B1 metabolize PAHs to DNA-reactive metabolites, the hepatic CYP1A2, however, may protect against lung tumor development by suppressing both liver and lung CYP1A1 enzymes. Further analysis of these enzymes has shown that PAH-exposure also induces sustained transcription of CYP1A1, which is independent of the persistence of the parent PAH. CYP1A2 enzyme plays an important role in the sustained induction of hepatic CYP1A1. PAH exposure may further contribute to pulmonary carcinogenesis by producing epigenetic alterations. DNA methylation, histone modification, long interspersed nuclear element (LINE-1) activation, and non-coding RNA, specifically microRNA (miRNA) alterations may all be induced by PAH exposure. The relationship between PAH-induced enzymatic reactive metabolite formation and epigenetic alterations is a key area of research that warrants further exploration. Investigation into the potential interplay between these two mechanisms may lead to further understanding of the mechanisms of PAH carcinogenesis. These mechanisms will be crucial for the development of effective targeted therapies and early diagnostic tools.

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Research works printed but not linked: 25

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Metadata

Authors
Stading, R., Gastelum, G., Chu, C., Jiang, W., & Moorthy, B.
Venue
Seminars in Cancer Biology
Publisher
Elsevier BV
Published
2021-11
Volume
76
Pages
3-16
ISSN
1044-579X (ISSN-L)
DOI
10.1016/j.semcancer.2021.07.001
OpenAlex
W3181023185
Cited by
253
References
100
FWCI
12.53
Type
journal article
Language
en
Open access
green
Licence
Funders
  • Cancer Prevention and Research Institute of Texas
  • U.S. Public Health Service (5R01ES 009132, RP190279)
  • Baylor College of Medicine (1P42 ES0327725, 1R01ES029382, R01HL129794)

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CoChat. (2026). Citation check: Molecular mechanisms of pulmonary carcinogenesis by polycyclic aromatic hydrocarbons (PAHs): Implications for human lung cancer. https://app.cochat.ai/papers/10.1016/j.semcancer.2021.07.001
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Stading, R., Gastelum, G., Chu, C., Jiang, W., & Moorthy, B. (2021). Molecular mechanisms of pulmonary carcinogenesis by polycyclic aromatic hydrocarbons (PAHs): Implications for human lung cancer. Seminars in Cancer Biology. https://doi.org/10.1016/j.semcancer.2021.07.001

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