ISSN:
0730-2312
Keywords:
intermediate biomarkers
;
chemoprevention
;
biological
;
molecular
;
genetic changes
;
hamster
;
buccal pouch
;
Life and Medical Sciences
;
Cell & Developmental Biology
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
Notes:
The Syrian golden hamster cheek pouch carcinogenesis model is probably the best-known animal system that closely compares to events involved in the development of premalignant and malignant human oral cancers. Furthermore, it is one of the most well-characterized models for squamous cell carcinomas (SCCs). However, stages of carcinogenesis (initiation, promotion, and progression) have not been well-defined in this system. Basic understanding of the mechanism(s) of carcinogenesis in this organ is instrumental for the development of new strategies for chemoprevention and early chemointervention. To understand the important early events that occur in the hamster cheek pouch carcinogenesis model, we compared it to the mouse skin model, where a number of critical events have been well characterized. We determined that approximately 60% of the hamster cheek pouch SCCs have a mutation in codon 61 of the Ha-ras gene. We also established a two-stage carcinogenesis protocol in this model using a single dose of dimethylbenz(a)anthracene (DMBA) and multiple doses of benzoyl peroxide for 45 weeks. Twenty-five percent of tumors developed with this protocol had the same mutation in codon 61 of the Ha-ras gene, confirming that this mutation, as in the mouse skin model, is initiation-related. We examined the sequential expression of hyperplasia, micronucleated cells, ornithine decarboxylase (ODC) activity, polyamine levels, transglutaminase I activity, epidermal growth factor receptor (EGF-R) levels, keratins, γ-glutamyltranspeptidase (GGT), transforming growth factor -β1 (TGF-β1), leukoplakia, and carcinomas induced during carcinogenesis. A number of these important biological molecular and genetic markers could be excellent intermediate endpoints in assessing the effects of various chemopreventive agents to be tested in the hamster cheek pouch model and in human clinical trials.
Additional Material:
4 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/jcb.240531012
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