Document Detail


Involvement of cell cycle control in bleomycin-induced mutagen sensitivity.
MedLine Citation:
PMID:  12203399     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bleomycin-induced chromosomal instability, generally referred to as mutagen sensitivity, is associated with an increased risk for the development of environmentally related cancer including head and neck squamous cell carcinoma and lung cancer. On average, the cultured lymphocytes of patients with these types of cancer show an increased number of chromatid breaks per cell after bleomycin exposure in the late S or G2 phase of the cell cycle as compared to lymphocytes from control persons. The aim of the present study was to investigate whether cell cycle regulation is involved in mutagen sensitivity. We determined cell cycle arrest after bleomycin-induced DNA damage in 21 lymphoblastoid cell lines that varied in mutagen sensitivity score. An ataxia telangiectasia (AT) cell line was included for comparison. Using a cut-off point of 0.70 breaks per cell, eight cell lines were classified as insensitive and 13 cell lines showed the hypersensitive phenotype. Compared to insensitive cell lines, bleomycin-treated hypersensitive cells remained at a relatively high level of DNA synthesis, as measured by thymidine incorporation, and showed a decreased accumulation of cells in G2 and M phase, as measured by flow cytometry. AT cells showed an extremely high mutagen sensitivity score, a high level of DNA synthesis, and a strong G2 block. In conclusion, mutagen sensitivity is associated with "damage-resistant growth," which is indicative of impaired cell cycle arrest. By which specific pathway(s) this checkpoint defect is explained has yet to be elucidated; however, it is probably distinct from the checkpoint defect in AT cells. Environ. Mol. Mutagen. 40:79-84, 2002.
Authors:
Jacqueline Cloos; Olaf Temmink; Manon Ceelen; Mireille H J Snel; Charles R Leemans; Boudewijn J M Braakhuis
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Environmental and molecular mutagenesis     Volume:  40     ISSN:  0893-6692     ISO Abbreviation:  Environ. Mol. Mutagen.     Publication Date:  2002  
Date Detail:
Created Date:  2002-08-30     Completed Date:  2002-10-04     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  8800109     Medline TA:  Environ Mol Mutagen     Country:  United States    
Other Details:
Languages:  eng     Pagination:  79-84     Citation Subset:  IM    
Copyright Information:
Copyright 2002 Wiley-Liss, Inc.
Affiliation:
Section Tumor Biology, Department of Otolaryngology/Head and Neck Surgery, Vrije Universiteit Medical Center, Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Bleomycin / toxicity*
Cell Cycle / drug effects,  physiology*
Cell Division / drug effects
Chromatids / drug effects
Chromosome Aberrations*
DNA Damage*
Flow Cytometry
G2 Phase / drug effects
Humans
Lymphocytes / cytology,  drug effects,  pathology*
Mitosis / drug effects
Mutagens / toxicity*
Reference Values
Thymidine / metabolism
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Mutagens; 11056-06-7/Bleomycin; 50-89-5/Thymidine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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