Role of retinoic acid in the modulation of benzo(a)pyrene-DNA adducts in human hepatoma cells: Implications for cancer prevention

Guo-Dong Zhou; Molly Richardson; Inayat S. Fazili; Jianbo Wang; Kirby C. Donnelly; Fen Wang; Brad Amendt; Bhagavatula Moorthy

doi:10.1016/j.taap.2010.09.019

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Role of retinoic acid in the modulation of benzo(a)pyrene-DNA adducts in human hepatoma cells: Implications for cancer prevention

Journal article

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Role of retinoic acid in the modulation of benzo(a)pyrene-DNA adducts in human hepatoma cells: Implications for cancer prevention

Guo-Dong Zhou, Molly Richardson, Inayat S. Fazili, Jianbo Wang, Kirby C. Donnelly, Fen Wang, Brad Amendt and Bhagavatula Moorthy

Toxicology and applied pharmacology, Vol.249(3), pp.224-230

2010

DOI: 10.1016/j.taap.2010.09.019

PMCID: PMC3001276

PMID: 20888851

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https://www.ncbi.nlm.nih.gov/pmc/articles/3001276View

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Abstract

Carcinogen-DNA adducts could lead to mutations in critical genes, eventually resulting in cancer. Many studies have shown that retinoic acid (RA) plays an important role in inducing cell apoptosis. Here we have tested the hypothesis that levels of carcinogen-DNA adducts can be diminished by DNA repair and/or by eliminating damaged cells through apoptosis. Our results showed that the levels of total DNA adducts in HepG2 cells treated with benzo(a)pyrene (BP, 2 μM) + RA (1 μM) were significantly reduced compared to those treated with BP only ( P = 0.038). In order to understand the mechanism of attenuation of DNA adducts, further experiments were performed. Cells were treated with BP (4 μM) for 24 h to initiate DNA adduct formation, following which the medium containing BP was removed, and fresh medium containing 1 μM RA was added. The cells were harvested 24 h after RA treatment. Interestingly, the levels of total DNA adducts were lower in the BP/RA group (390 ± 34) than those in the BP/DMSO group (544 ± 33), P = 0.032. Analysis of cell apoptosis showed an increase in BP + RA group, compared to BP or RA only groups. Our results also indicated that attenuation of BP-DNA adducts by RA was not primarily due to its effects on CYP1A1 expression. In conclusion, our results suggest a mechanistic link between cellular apoptosis and DNA adduct formation, phenomena that play important roles in BP-mediated carcinogenesis. Furthermore, these results help understand the mechanisms of carcinogenesis, especially in relation to the chemopreventive properties of nutritional apoptosis inducers.

32P-Postlabeling assay

Apoptosis

Benzo(a)pyrene

DNA adducts

DNA repair

HepG2

Details

Title: Subtitle: Role of retinoic acid in the modulation of benzo(a)pyrene-DNA adducts in human hepatoma cells: Implications for cancer prevention
Creators: Guo-Dong Zhou - Department of Environmental and Occupational Health, School of Rural Public Health, Texas A&M University System, College Station, Texas, USA
Molly Richardson - Texas A&M University System
Inayat S. Fazili - Baylor College of Medicine
Jianbo Wang - Texas A&M University System
Kirby C. Donnelly - Texas A&M University System
Fen Wang - Texas A&M University System
Brad Amendt - Texas A&M University System
Bhagavatula Moorthy - Baylor College of Medicine
Resource Type: Journal article
Publication Details: Toxicology and applied pharmacology, Vol.249(3), pp.224-230
DOI: 10.1016/j.taap.2010.09.019
PMID: 20888851
PMCID: PMC3001276
NLM abbreviation: Toxicol Appl Pharmacol
ISSN: 0041-008X
eISSN: 1096-0333
Publisher: Elsevier Inc
Language: English
Date published: 2010
Academic Unit: Orthodontics; Anatomy and Cell Biology; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9984284337102771

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