Document Detail


Initiation of genetic instability and tumour formation: a review and hypothesis of a nongenotoxic mechanism.
MedLine Citation:
PMID:  12861379     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Genetic instability in tumours results in cell-to-cell variability of genome which parallels the cell-to-cell variability of microscopic morphology and of behaviour (tumour cell heterogeneity) of these lesions. Genetic instability is therefore strongly supported as the fundamental process by which normal tissue cells become neoplastic. The commonest current suggestion for the mechanism of initiation of carcinogenesis is a 'direct hit' mutation of a 'cancer critical' gene in a somatic cell by carcinogenic agents. However, this mechanism does not account for the activity of carcinogens which are not mutagens, and does not explain why many mutagens are not carcinogens. This paper proposes a nonmutational (nongenotoxic) mechanism of initiation of genetic instability in previously normal cells as follows: 1) During S phase of local tissue stem cells, carcinogen binds to and disables the proofreading enzyme for a new DNA strand. 2) While it is disabled, the proofreading enzyme fails to correct illicit changes in the nucleotide sequence(s) for one or more genes for proofreading fidelity or repair of DNA in the new strand of DNA, which passes to one daughter cell. 3) When this daughter cell is a continuing stem cell, the resulting cell line remains immortal, and retains its prior differentiation commitment to produce daughter cells of a particular type. However, the acquired genetic instability in this cell line causes secondary mutations which lead to uncontrolled growth, and the heterogeneous morphologic and behavioural features of a tumour resembling the parent cell type.
Authors:
L P Bignold
Related Documents :
10423829 - Ideas in theoretical biology. origin of cancerous cells from tumours.
20959439 - Expression of connective tissue growth factor and igf1 in normal and neoplastic gastroi...
2561999 - Effector-target co-aggregation as a crucial step in the neutrophil-mediated tumour cell...
15050959 - Tumour-cell migration, invasion, and metastasis: navigation by neurotransmitters.
15452169 - Large cell neuroendocrine carcinoma of the ampulla of vater with glandular differentiat...
115209 - Histochemical patterns in human breast tumours.
21472349 - Allyl isothiocyanate induces g2/m arrest in human colorectal adenocarcinoma sw620 cells...
1315239 - Phorbol esters inhibit ionomycin-induced hydrolysis of phosphoinositides and phosphatid...
23454129 - Serum amyloid a stimulates macrophage foam cell formation via lectin-like oxidized low-...
Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Cellular and molecular life sciences : CMLS     Volume:  60     ISSN:  1420-682X     ISO Abbreviation:  Cell. Mol. Life Sci.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-07-15     Completed Date:  2003-08-05     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  9705402     Medline TA:  Cell Mol Life Sci     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  1107-17     Citation Subset:  IM    
Affiliation:
Department of Pathology, University of Adelaide, SA 5005, Australia. leon.bignold@adelaide.edu.au
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Carcinogens / toxicity
Cell Division / drug effects,  genetics
Cocarcinogenesis
Humans
Mitosis / drug effects
Models, Biological
Mutagens / toxicity
Mutation
Neoplasms / etiology*,  genetics*,  pathology
Stem Cells / drug effects
Chemical
Reg. No./Substance:
0/Carcinogens; 0/Mutagens

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


Previous Document:  Rethinking synchronization of mammalian cells for cell cycle analysis.
Next Document:  Isoprenoid biosynthesis in hereditary periodic fever syndromes and inflammation.