Progression of 1,2-Dimethylhydrazine-Induced Colonic Pathological Lesions In Albino Rats: An Experimental Model

Colorectal cancer (CRC) is a widespread malignant neoplasm kill millions of people worldwide. 1,2-dimethylhydrazine (DMH) is a potent carcinogen used for induction of a CRC model mirroring the pathological features of various stages of colorectal carcinogenesis in human sporadic CRC. However, various steps involving CRC by DMH are poorly defined. Therefore, this study aimed to characterize the multistep progression of colonic lesions and associated immunohistochemical markers during DMH-induced CRC development. Fifty rats were allocated into 2 groups: 25 rats in the control group and 25 rats in the DMH group. Each rat in the DMH group was administered DMH (40 mg/kg body weight I/P) once weekly for 12 weeks, and 5 rats were euthanized from both groups at 8, 12, 16, 20, and 24 weeks from the first DMH treatment. Hyperplasia, low grade dysplasia and high grade dysplasia were detected in DMH exposed group at 8,12 and 16 weeks post exposure respectively. Advanced and invasive carcinoma were also detected at 20 and 24 weeks post exposure. In addition, immunohistochemical analysis revealed a decrease in caspase-3 expression and an increase in β-catenin expression in the colonic sections. In conclusion, the macroscopic mucosal elevations could be detected after 16 weeks of DMH exposure. Additionally, the microscopic preneoplastic dysplastic lesions started at 12 weeks while the typical neoplastic changes could be noticed at 20 weeks post exposure. Subsequently, knowing the time dependent changes and the associated molecular targets could be a key approach to treat CRC.