Document Detail


Hydrocarbon carcinogens evade cellular defense mechanism of G1 arrest in nontransformed and malignant lung cell lines.
MedLine Citation:
PMID:  11384212     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Q A Khan; L M Anderson
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Toxicology and applied pharmacology     Volume:  173     ISSN:  0041-008X     ISO Abbreviation:  Toxicol. Appl. Pharmacol.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-05-31     Completed Date:  2001-06-21     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0416575     Medline TA:  Toxicol Appl Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  105-13     Citation Subset:  IM    
Affiliation:
Cellular Pathogenesis Section, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA. khanq@mail.nih.gov
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MeSH Terms
Descriptor/Qualifier:
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / 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:
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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