Document Detail

Food restriction eliminates preneoplastic cells through apoptosis and antagonizes carcinogenesis in rat liver.
MedLine Citation:
PMID:  7937932     Owner:  NLM     Status:  MEDLINE    
Restriction of dietary calories reduces cancer formation in experimental animals and probably also in humans. This effect is generally attributed to the inhibitory effect of fasting on cell proliferation. Here we studied the effect of fasting on physiological cell death through apoptosis by using rat liver as a model. (i) In normal liver, involution of hyperplasia by apoptosis was reinforced by food withdrawal and suppressed by feeding. Complete food withdrawal for 8 days or food reduction by 40% for 3 months eliminated 20-30% of normal liver cells through apoptosis. (ii) Putative preneoplastic liver foci exhibited severalfold higher rates of DNA replication and apoptosis than unaltered liver. Food restriction lowered DNA replication but increased apoptosis, which reduced the number and volume of putative preneoplastic liver foci by 85% within 3 months. Subsequent return to ad libitum feeding normalized cell replication and apoptosis but clear differences in the volume and number of putative preneoplastic liver foci persisted throughout the following 17 months. Treatment of animals after food restriction with nafenopin, a peroxisome proliferator and potent tumor promoter, produced only half as many hepatocellular adenomas and carcinomas as in animals fed unrestrictedly throughout their lifetime. This indicates that food restriction had actually eliminated a part of the initiated cells. This study demonstrates that food restriction preferentially enhances apoptosis of preneoplastic cells. This effect in combination with lowered cell replication provides protection from carcinogenesis.
B Grasl-Kraupp; W Bursch; B Ruttkay-Nedecky; A Wagner; B Lauer; R Schulte-Hermann
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  91     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1994 Oct 
Date Detail:
Created Date:  1994-11-10     Completed Date:  1994-11-10     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  9995-9     Citation Subset:  IM    
Institut für Tumorbiologie-Krebsforschung, Vienna, Austria.
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MeSH Terms
Cell Division
Circadian Rhythm
Cyproterone Acetate / pharmacology*
DNA Replication / physiology*
Diet, Reducing*
Glutathione Transferase / analysis
Liver / drug effects,  metabolism,  pathology*
Liver Neoplasms / pathology,  prevention & control*
Nafenopin / pharmacology*
Precancerous Conditions / pathology*
Rats, Wistar
Time Factors
Tumor Markers, Biological / analysis
Reg. No./Substance:
0/Tumor Markers, Biological; 3771-19-5/Nafenopin; 427-51-0/Cyproterone Acetate; EC Transferase

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

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