Article

Animal model in the study of colorectal carcinogenesis.

University of Ljubljana, Medical Faculty, Institute of Pathology, Laboratory of Molecular Genetics, Slovenia.
Pflügers Archiv - European Journal of Physiology (impact factor: 4.46). 02/2000; 440(5 Suppl):R55-7. DOI:10.1007/s004240000005 pp.R55-7
Source: PubMed

ABSTRACT Experimental animal models of neoplastic diseases are important in understanding etiological and pathophysiological processes also in humans. In order to investigate whether the mechanism of genomic instability is associated with chemically induced colorectal tumorigenesis in rat we performed the following study: One hundred and fifty Wistar rats (males 220-280 g and females 140-180 g) were used in the study. Colorectal tumors were induced by means of 15 s.c. applications (20 mg/kg) of 1,2-dimethylhydrazine (DMH). On autopsy, all intestinal lesions were assessed by histological criteria used in human pathology. Forty five tumors were found in the large intestine--30 of these in males and 15 in females, i.e. in 27% of all animals. In four animals multiple primary tumors were found. Histologically 24 tumours were adenocarcinomas, 14 signet-cell carcinoma and 7 adenomas. DNA was extracted from rat neoplastic lesions and adjoining microscopically normal tissues from the same slide and amplified by PCR, using 10 different microsatellite markers from chromosomes 1, 3, 5, 7 and 8. PCR amplicon were analyzed for microsatellite instability with non-isotopic method. In 13 adenocarcinomas (29%) microsatellite instability was found at a minimum of 1 locus. Seven tumors (15.5%) showed microsatellite instability at multiple loci. The results of our experiment suggest that genomic instability is an important molecular event in the pathophysiology of DMH induced colorectal carcinogenesis in rats.

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Keywords

10 different microsatellite markers
 
13 adenocarcinomas
 
14 signet-cell carcinoma
 
15 s.c. applications
 
7 adenomas
 
adjoining microscopically normal tissues
 
animals multiple primary tumors
 
chemically induced colorectal tumorigenesis
 
chromosomes 1
 
Colorectal tumors
 
DMH induced colorectal carcinogenesis
 
genomic instability
 
Histologically 24 tumours
 
microsatellite instability
 
molecular event
 
neoplastic diseases
 
non-isotopic method
 
rat neoplastic lesions
 
understanding etiological
 
Wistar rats