Document Detail


Intraperitoneal injection of D-galactosamine provides a potent cell proliferation stimulus for the detection of initiation activities of chemicals in rat liver.
MedLine Citation:
PMID:  16208626     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In an in vivo 5-week initiation assay model, chemical hepatectomy by hepato-toxicant administration was utilized as a cell proliferation stimulus as an alternative to the two-thirds partial hepatectomy. The study investigated the effect of an intraperitoneal (i.p.) injection of D-galactosamine (D-gal) for this purpose in a medium-term liver bioassay, with a further focus on cell proliferation kinetics and cytochrome P450 (CYP) expression. In experiment I, cell proliferation in rat liver after a single administration of D-gal (700 mg kg(-1), i.p.) was analysed by the bromodeoxyuridine (BrdU) labeling method, and CYP isozymes were quantified by immunoblotting. In experiment II, the induction of glutathione S-transferase placental form (GST-P) positive foci by 1,2-dimethylhydrazine (DMH) was evaluated in a modified in vivo 5-week initiation assay model. At 84 hours after single administration of d-gal (i.p.) the BrdU index was markedly elevated (27.5% +/- 9.5%). Although CYP 2E1 and 1A2 apoprotein contents decreased transiently to less than 20% of the control level, subsequently they recovered to 60% and 40% of the control level, respectively, at 84 hours. Induction of GST-P positive foci in the group given DMH at 84 hours after a single administration of d-gal was significantly greater than in the control group, correlating with the kinetics of cell proliferation. In conclusion, the sensitivity of the present initiation assay using D-gal i.p. is high, so that D-gal i.p. can be considered an effective cell proliferation stimulus.
Authors:
Yoshiji Asaoka; Hiroki Sakai; Naofumi Takahashi; Akihiro Hirata; Tetsuya Tsukamoto; Masami Yamamoto; Tokuma Yanai; Toshiaki Masegi; Masae Tatematsu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of applied toxicology : JAT     Volume:  25     ISSN:  0260-437X     ISO Abbreviation:  J Appl Toxicol     Publication Date:    2005 Nov-Dec
Date Detail:
Created Date:  2005-11-01     Completed Date:  2006-12-04     Revised Date:  2014-01-10    
Medline Journal Info:
Nlm Unique ID:  8109495     Medline TA:  J Appl Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  554-61     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2005 John Wiley & Sons, Ltd.
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MeSH Terms
Descriptor/Qualifier:
1,2-Dimethylhydrazine / administration & dosage,  toxicity*
Animals
Carcinogenicity Tests
Cell Proliferation / drug effects
Cytochrome P-450 CYP1A2 / metabolism
Cytochrome P-450 CYP2E1 / metabolism
Cytochrome P-450 Enzyme System / metabolism*
Cytochromes
Drug Synergism
Enzyme Induction
Galactosamine / administration & dosage,  toxicity*
Glutathione Transferase / biosynthesis*
Immunohistochemistry
Injections, Intraperitoneal
Liver / drug effects*,  metabolism,  pathology
Liver Neoplasms, Experimental / etiology*,  metabolism,  pathology
Male
Precancerous Conditions / etiology*,  metabolism,  pathology
Rats
Rats, Inbred F344
Chemical
Reg. No./Substance:
0/Cytochromes; 7535-00-4/Galactosamine; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.14.1/Cyp1a2 protein, rat; EC 1.14.14.1/Cytochrome P-450 CYP1A2; EC 1.14.14.1/Cytochrome P-450 CYP2E1; EC 2.5.1.18/Glutathione Transferase; IX068S9745/1,2-Dimethylhydrazine

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


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