Document Detail


A comparison of intraperitoneal and oral gavage administration in comet assay in mouse eight organs.
MedLine Citation:
PMID:  11516714     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
One of the important advantages of the comet assay is its ability to detect genotoxicity in many different organs. Since the exposure route of the test compounds is likely to influence the genotoxicity detected in a given organ, it is an important factor to consider when conducting the assay. In this study, we compared the effects of numerous model compounds on eight organs when administered to mice by intraperitoneal (i.p.) injection and oral (p.o.) gavage. Groups of four mice were treated once i.p. or p.o. at the identical proportion of LD50 for each route, and the stomach, colon, liver, kidney, bladder, lung, brain, and bone marrow were sampled 3, 8, and 24h after treatment. For 19 of the 20 tested mutagens with various modes of action, genotoxicity in some organs varied with treatment route; only the genotoxicity of methyl methane sulfonate was not affected. Treatment route, however, did not produce a qualitative difference in the genotoxicity of promutagens at the sites of conversion to ultimate mutagens, with aromatic hydrocarbons as the exception. When chemicals with positive responses in at least one organ were considered to be comet assay-positive, the administration route made no difference. Since azo reduction is mediated by azo reductase synthesized in the gastrointestinal wall and by gut microflora and i.p.-administered azo dyes bypass their activation site (colon), the administration route is expected to make a difference in their in vivo genotoxicity. Direct-acting mutagens are expected to affect the mucosa of the gastrointestinal tract when given p.o. For those mutagens, however, the administration route did not make a qualitative difference in gastrointestinal tract genotoxicity. Moreover, although the gastrointestinal mucosa is the first site to be exposed to p.o. administered agents, the peak times in the stomach tended to be the same as in most other organs. Based on those results, we concluded that the genotoxicity at high exposures was due to a systemic effect, and that both routes are acceptable for the comet assay when the liver and gastrointestinal organs are sampled, so long as appropriate dose levels for systemic exposure are selected for each route.
Authors:
K Sekihashi; T Sasaki; A Yamamoto; K Kawamura; T Ikka; S Tsuda; Y F Sasaki
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Mutation research     Volume:  493     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2001 Jun 
Date Detail:
Created Date:  2001-08-22     Completed Date:  2001-09-13     Revised Date:  2009-11-03    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  39-54     Citation Subset:  IM    
Affiliation:
Laboratory of Genotoxicity, Faculty of Chemical and Biological Engineering, Hachinohe National College of Technology, Tamonoki Uwanotai 16-1, Hachinohe, Aomori 039-1192, Japan.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Alkylating Agents / administration & dosage,  toxicity
Amines / administration & dosage,  toxicity
Animals
Azo Compounds / administration & dosage,  toxicity
Comet Assay*
DNA Damage
Digestive System / drug effects
Hydrazines / administration & dosage,  toxicity
Hydrocarbons, Aromatic / administration & dosage,  toxicity
Injections, Intraperitoneal
Liver / drug effects
Male
Mice
Mutagens / administration & dosage*,  toxicity*
Organ Specificity
Salts / administration & dosage,  toxicity
Chemical
Reg. No./Substance:
0/Alkylating Agents; 0/Amines; 0/Azo Compounds; 0/Hydrazines; 0/Hydrocarbons, Aromatic; 0/Mutagens; 0/Salts

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


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