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Morphogenesis of colonic adenomas in mice treated with N,N'-dimethylhydrazine dihydrochloride
Abstract:
The morphogenesis of colonic adenomas in ICR mice treated with N,N'-dimethylhydrazine dihydrochloride (DMH) was studied. Treatment of 17 mice with DMH (20 mg/kg/week) for 24 weeks induced 100% incidence of multiple adenomas in the mucosa of the most distal 7 cm of the large intestine. These adenomas were composed of atypical epithelium of the absorptive cell type. Forty-two single atypical gland lesions (single gland adenomas) were detected in the upper part of the mucosa by serial sectioning. These single gland adenomas consisted of atypical epithelium with a narrow lumen and showed endophytic growth to the lamina propria mucosae. Complete serial sections also revealed that single gland adenomas had no direct continuity of the surrounding crypts of Lieberkühn. Single gland adenomas developed into microscopic adenomas consisting of several atypical glands by branching of the small atypical glands.
Insights
N,N'-dimethylhydrazine dihydrochloride (DMH) induced colonic adenomas in mice. These tumors originated from single atypical gland lesions, demonstrating endophytic growth and developing into multiple adenomas.
Area of Science:
- Gastroenterology
- Oncology
- Mouse models
Background:
- Colonic adenomas are precancerous lesions.
- Understanding adenoma morphogenesis is crucial for cancer prevention.
Purpose of the Study:
- To investigate the early morphogenesis of colonic adenomas induced by N,N omino-dimethylhydrazine dihydrochloride (DMH) in ICR mice.
- To characterize the initial cellular and structural changes leading to adenoma formation.
Main Methods:
- ICR mice were treated with DMH (20 mg/kg/week) for 24 weeks.
- Histopathological analysis using serial sectioning was performed on the distal colon.
- Morphological characteristics of induced lesions were documented.
Main Results:
- DMH treatment resulted in 100% incidence of multiple colonic adenomas in the distal colon.
- Single atypical gland lesions (single gland adenomas) were identified as early precursors.
- These lesions exhibited atypical epithelium, narrow lumens, and endophytic growth into the lamina propria.
- Single gland adenomas showed no continuity with surrounding crypts and developed into microscopic adenomas via branching.
Conclusions:
- DMH-induced colonic adenomas originate from distinct single atypical gland lesions.
- These early lesions undergo specific growth patterns to form macroscopic adenomas.
- The study elucidates the initial steps in colonic adenoma development in a mouse model.