Document Detail


Rapid in vivo assay for topical oral cancer chemopreventive agents.
MedLine Citation:
PMID:  12063563     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The cancer chemopreventive effect of topically applied phenethyl isothiocyanate (PEIT) was examined in a hamster buccal pouch model, in which squamous cell carcinomas (SCC) are induced at high frequency, by topical application of N-methyl-N-benzylnitrosamine (MBN). The buccal pouches of eleven hamsters were pretreated thrice-weekly for two weeks with corn oil (CO) containing 50 mM PEIT, followed by 22 weeks of twice-weekly application of CO containing MBN and PEIT, both at 50 mM. Under similar conditions, twelve hamsters were pretreated with CO for 2 weeks, followed by MBN in CO. Tumor analysis was performed 19 days after the last application of PEIT and MBN. The incidence of tumors (approximately 90% SCC) in the unprotected and protected groups was 100% and 73%, respectively. Although total tumor incidence was marginally decreased, PEIT inhibited significantly the tumor frequency and tumor burden by 79% and 74%, respectively. In both groups, 43% of the carcinomas exhibited p53 immunohistochemical activity. A short-term experiment was performed to determine whether PEIT inhibits MBN-induced cellular foci expressing gamma-glutamyltranspeptidase histochemical activity (gamma-GT foci). Buccal pouches of four protected hamsters received 50 mM PEIT pretreatment on days 1 and 4, followed on days 6 and 9 by application of CO containing MBN and PEIT, both at 50 mM. Four unprotected hamsters were similarly pretreated with CO, followed by MBN in CO. gamma-GT foci were enumerated in buccal pouch epithelial whole mounts prepared from pairs of protected and unprotected hamsters on days 10 through 13. Whereas the number of gamma-GT foci in unprotected hamsters ranged from 98 to 356 per 10 cm2, the protected hamsters exhibited no more than one focus per 10 cm2. This model may be useful for rapid identification of chemopreventive agents, and combinations of agents, which inhibit initiation and promotion stages of oral carcinogenesis.
Authors:
Khaled Shabany; Pei-Ching Chiu; Ardeshir Raghian; Kuo-Wei Chang; Dennis B Solt
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  International journal of oncology     Volume:  21     ISSN:  1019-6439     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-06-13     Completed Date:  2002-12-02     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  159-64     Citation Subset:  IM    
Affiliation:
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611, USA.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Aldehyde Dehydrogenase / antagonists & inhibitors
Animals
Biological Assay / methods
Carcinogens / toxicity
Carcinoma, Squamous Cell / chemically induced,  metabolism,  prevention & control*
Corn Oil
Cricetinae
Dimethylnitrosamine / analogs & derivatives*,  toxicity
Genes, p53 / drug effects,  genetics
Isothiocyanates / administration & dosage,  therapeutic use*
Male
Mesocricetus
Mouth Mucosa / drug effects,  metabolism
Mouth Neoplasms / chemically induced,  metabolism,  prevention & control*
gamma-Glutamyltransferase / metabolism
Grant Support
ID/Acronym/Agency:
1 R03 CA89788-01A1/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Carcinogens; 0/Isothiocyanates; 2257-09-2/phenethyl isothiocyanate; 62-75-9/Dimethylnitrosamine; 8001-30-7/Corn Oil; 937-40-6/nitrosobenzylmethylamine; EC 1.2.1.3/Aldehyde Dehydrogenase; EC 2.3.2.2/gamma-Glutamyltransferase

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


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