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Enzyme-altered foci in colons of carcinogen-treated rats
B J Barrow1, M A O'Riordan, T A Stellato
1Department of Pathology, Case Western Reserve University Medical School, Cleveland, Ohio 44106.
Abstract:
The distal colon and rectum from male F344 rats treated with 15 mg/kg 1,2-dimethylhydrazine.2HCl (DMH) for 20 weeks were analyzed for focal areas of enzyme alteration. Tissues were embedded in methacrylate at 4 degrees C and cut in 2- to 4-micron serial sections. In DMH-treated rats, 8.8 +/- 2.4 foci/cm2 of examined mucosa were observed at 20 weeks and 7.7 +/- 1.1 foci/cm2 at 31 to 52 weeks, compared with 1.2 +/- 0.6 foci/cm2 in control rats (P = 0.01). The number of foci at 31 to 52 weeks compared with 20 weeks did not change significantly, but the area of altered rectal mucosa increased from 0.22 +/- 0.2% at 20 weeks to 1.47 +/- 0.6% at 31 to 52 weeks (P = 0.051). Most foci had decreased N-acetyl-beta-D-glucosaminidase, alpha-naphthyl butyrate esterase, and mucin in epithelial cells and increased gamma-glutamyl transpeptidase in the stroma. Morphologically, the foci varied from normal to overtly dysplastic. Grossly, tumors were identified in 5 of 20 DMH-treated rats killed at 31 to 52 weeks but not in 12 DMH-treated rats killed at 20 weeks or 30 control rats killed at 20 to 52 weeks. These data suggest but do not establish that enzyme-altered foci are putative preneoplastic lesions in the colon.
Insights
1,2-dimethylhydrazine (DMH) induced focal enzyme alterations in rat colon and rectum tissues. These enzyme-altered foci are suggested as potential preneoplastic lesions, with some DMH-treated rats developing tumors over time.
Area of Science:
- Gastroenterology
- Oncology
- Toxicology
Background:
- 1,2-dimethylhydrazine (DMH) is a chemical carcinogen used to induce colorectal cancer in animal models.
- Understanding early preneoplastic changes is crucial for developing effective cancer prevention strategies.
Purpose of the Study:
- To investigate the presence and characteristics of enzyme-altered foci in the distal colon and rectum of rats treated with DMH.
- To evaluate the potential of these foci as preneoplastic lesions in chemical-induced colorectal carcinogenesis.
Main Methods:
- Male F344 rats were administered DMH (15 mg/kg) for 20 weeks.
- Distal colon and rectal tissues were analyzed for focal areas of enzyme alteration using serial sections.
- Enzyme activities (N-acetyl-beta-D-glucosaminidase, alpha-naphthyl butyrate esterase, mucin, gamma-glutamyl transpeptidase) and morphological changes were assessed.
Main Results:
- DMH-treated rats exhibited significantly more enzyme-altered foci (8.8 foci/cm2) compared to controls (1.2 foci/cm2) at 20 weeks.
- The area of altered rectal mucosa increased from 0.22% at 20 weeks to 1.47% by 31-52 weeks.
- Most foci showed decreased epithelial enzymes/mucin and increased stromal gamma-glutamyl transpeptidase; tumors were observed in 5/20 DMH-treated rats at later time points.
Conclusions:
- Enzyme-altered foci in the rat colon and rectum following DMH treatment display characteristics suggestive of preneoplastic lesions.
- Further studies are needed to definitively establish these foci as preneoplastic and to understand their progression to tumors.