Document Detail

Cell proliferation rates in common cancer target tissues of B6C3F1 mice and F344 rats: effects of age, gender, and choice of marker.
MedLine Citation:
PMID:  8921319     Owner:  NLM     Status:  MEDLINE    
Increasing emphasis is being placed on mode of action for chemical carcinogens as an important consideration for risk assessment. Many rodent carcinogens appear to act through nongenotoxic mechanisms, such as induced cell proliferation. Information on cell proliferation rates based on species, age, gender, tissue, and choice of marker will provide a foundation for incorporating such measurements into rodent toxicity studies. Cell proliferation was evaluated in liver, kidney, skin, and forestomach of control male and female B6C3F1 mice and F344 rats at 7, 10, 13, and 20 weeks of age. Proliferating cell nuclear antigen (PCNA), an endogenous cell proliferation marker, and bromodeoxyuridine (BrdU) administered by ip injection 2 hr before euthanization were compared as markers of cell proliferation. Only in liver were BrdU and PCNA labeling indices (LIs; S phase only) statistically similar. As expected, the PCNA proliferating index (PI; G1 + S + G2 + M phases) was consistently greater than the S phase LI in all tissues examined. Age-related differences in LI were evident in liver and kidney, whereas LIs in the forestomach and skin were not age- dependent. In all tissues examined, gender- and species-related differences in cell proliferation were detected. Although BrdU and PCNA LIs were often statistically different, they both provided a useful indication of cell proliferation rates in the tissues examined. These results provide potentially useful information for designing rodent toxicity studies and biological models of carcinogenesis.
S R Eldridge; S M Goldsworthy
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Fundamental and applied toxicology : official journal of the Society of Toxicology     Volume:  32     ISSN:  0272-0590     ISO Abbreviation:  Fundam Appl Toxicol     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1997-03-12     Completed Date:  1997-03-12     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8200838     Medline TA:  Fundam Appl Toxicol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  159-67     Citation Subset:  IM    
Pathology Associates International, Durham, North Carolina 27713, USA.
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MeSH Terms
Age Factors
Biological Markers
Bromodeoxyuridine / analysis
Cell Cycle*
Cell Division*
Kidney / cytology
Liver / cytology
Proliferating Cell Nuclear Antigen / analysis
Rats, Inbred F344
Sex Factors
Skin / cytology
Stomach / cytology
Grant Support
1R43CA6280-01/CA/NCI NIH HHS
Reg. No./Substance:
0/Biological Markers; 0/Proliferating Cell Nuclear Antigen; 59-14-3/Bromodeoxyuridine

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

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