| Hydrocarbon carcinogens evade cellular defense mechanism of G1 arrest in nontransformed and malignant lung cell lines. | |
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MedLine Citation:
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PMID: 11384212 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In previous studies using human breast carcinoma cells (MCF-7) and human colon carcinoma cells (RKO) we have shown that, in response to treatment with hydrocarbon carcinogens, these cell lines failed to undergo a p53-mediated cell cycle arrest in G1 phase; rather, the cells were accumulated in the S phase with damaged DNA, a situation that may lead to replication of DNA on a damaged template, resulting in the enhanced frequency of mutations in the daughter cells. This has been termed a stealth effect. In the present work we have demonstrated that the stealth effect also pertains for lung cells. In E10 nontransformed mouse lung type II cells, two potent hydrocarbon carcinogens, benzo[a]pyrene dihydrodiol epoxide and benzo[g]chrysene dihydrodiol epoxide, damaged DNA as suggested by retardation in S phase, but did not cause G1 arrest, in contrast to the positive control, actinomycin D. Human lung adenocarcinoma A549 cells, with normal p53, likewise exhibited G1 arrest after actinomycin D, but not after treatment with the diol epoxides. Several human lung cancer cell lines with absent or mutant p53, such as H358, H1734, and H82, exhibited no G1 arrest after any of the compounds. However, lung H441 adenocarcinoma cells, with a mutation in exon 5, codon 158 of p53, exhibited partial G1 arrest after the diol epoxides as well as actinomycin D, and H2030 adenocarcinoma cells did not show G1 arrest after any of the chemicals despite a normal p53. The stealth effect of evasion of G1 arrest may contribute to initiation of lung adenocarcinomas and to progression of tumors. A role in resistance to chemotherapy by certain drugs is also likely. |
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Authors:
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Q A Khan; L M Anderson |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Toxicology and applied pharmacology Volume: 173 ISSN: 0041-008X ISO Abbreviation: Toxicol. Appl. Pharmacol. Publication Date: 2001 Jun |
Date Detail:
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Created Date: 2001-05-31 Completed Date: 2001-06-21 Revised Date: 2004-11-17 |
Medline Journal Info:
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Nlm Unique ID: 0416575 Medline TA: Toxicol Appl Pharmacol Country: United States |
Other Details:
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Languages: eng Pagination: 105-13 Citation Subset: IM |
Affiliation:
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Cellular Pathogenesis Section, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. khanq@mail.nih.gov |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
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toxicity* Adenocarcinoma / genetics, pathology* Adenocarcinoma, Bronchiolo-Alveolar / genetics, pathology Animals Antineoplastic Agents / pharmacology Carcinogens / toxicity* Cell Line Cell Transformation, Neoplastic / chemically induced*, genetics, pathology Chrysenes / toxicity* DNA Damage Dactinomycin / pharmacology Epithelial Cells / drug effects Flow Cytometry G1 Phase / drug effects, physiology* Genes, p53 / genetics Humans Lung / cytology, drug effects*, physiology Lung Neoplasms / genetics, pathology* Mice Mutagens / toxicity Mutation Nocodazole / pharmacology Nucleic Acid Synthesis Inhibitors / pharmacology Tumor Cells, Cultured / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Carcinogens; 0/Chrysenes; 0/Mutagens; 0/Nucleic Acid Synthesis Inhibitors; 132832-27-0/benzo(g)chrysene-11,12-dihydrodiol-13,14-epoxide; 31430-18-9/Nocodazole; 50-76-0/Dactinomycin; 55097-80-8/7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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