Document Detail


Sensitivity analysis of a new model of carcinogenesis.
MedLine Citation:
PMID:  1296096     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A new simulation model of carcinogenesis is described which, in addition to the features of a standard clonal two-stage model (loss of both copies of a tumor suppressor gene by point mutations, cell division and cell death), includes a quantitative description of mitotic recombination, DNA repair, and cell to cell interactions in all stages. The model is implemented as a discrete event process. The results of a sensitivity analysis of the model are presented. The most sensitive parameters were found to be: the number of normal cells at risk, and the division rate, death rate and DNA repair efficiency for the intermediate stage cells. Accurate information about these parameters is important for a quantitative understanding of carcinogenesis. The sensitivity of the model to the number of normal cells indicates the importance of understanding the nature of the cells at risk, for example, stem cells vs. differentiated cells. The model can be used to assess the importance of chromosomal damage such as mitotic recombination and epigenetic mechanisms such as hyperplasia and cytotoxicity in the onset of malignant tumors.
Authors:
F Y Bois; P J Compton-Quintana
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of theoretical biology     Volume:  159     ISSN:  0022-5193     ISO Abbreviation:  J. Theor. Biol.     Publication Date:  1992 Dec 
Date Detail:
Created Date:  1993-04-22     Completed Date:  1993-04-22     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0376342     Medline TA:  J Theor Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  361-75     Citation Subset:  IM    
Affiliation:
Indoor Environment Program, Lawrence Berkeley Laboratory, CA 94720.
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MeSH Terms
Descriptor/Qualifier:
Cell Death / physiology
Cell Division / physiology
Genes, Tumor Suppressor / genetics*
Humans
Models, Genetic*
Neoplasms / genetics*
Neoplastic Stem Cells / physiology
Sensitivity and Specificity
Grant Support
ID/Acronym/Agency:
CA39910/CA/NCI NIH HHS; ES04705/ES/NIEHS NIH HHS

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


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