Optimization of DMH-Induced Colorectal Carcinogenesis in Rats: A Systematic Meta-Review

Colorectal cancer (CRC) remains a major global health concern, and experimental animal models continue to play a key role in understanding its development and in evaluating preventive and therapeutic strategies. Among these, the 1,2-dimethylhydrazine (DMH)-induced rat model is widely used; however, substantial variability in dosing regimens and study design has limited consistency across studies. The present systematic review aimed to synthesize existing evidence on DMH-induced colorectal carcinogenesis in rats, with particular attention to how dose, duration, and route of administration influence pathological outcomes. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science from January 2010 to December 2025. Eligible studies were screened and analyzed based on predefined inclusion criteria. Data were extracted on induction protocols, histopathological findings, and study characteristics. Across the 430 included studies, notable heterogeneity was observed in experimental protocols. Nevertheless, certain patterns emerged. Higher-dose, shorter-duration regimens were more frequently associated with early preneoplastic lesions such as aberrant crypt foci (ACF), whereas lower-dose, longer-duration protocols tended to be linked with more advanced tumor development. Subcutaneous administration appeared to provide more consistent results compared to other routes. These findings suggest that the choice of protocol should be guided by the intended stage of carcinogenesis under investigation. Importantly, the interpretation of these findings should be approached with caution. Many studies lacked detailed reporting of methodological parameters, and quantitative synthesis was limited by incomplete data. As such, the proposed framework should be viewed as a practical guide rather than a definitive standard. In conclusion, DMH-induced CRC models in rats remain valuable but highly sensitive to experimental design. Greater standardization and more rigorous reporting are needed to improve reproducibility and strengthen the translational relevance of future studies.