Experimental Model of Rectal Carcinogenesis Induced by N-Methyl-N-Nitrosoguanidine in Mice with Endoscopic Evaluation

Int J Med Sci. 2020 Sep 10;17(16):2505-2510. doi: 10.7150/ijms.48231. eCollection 2020.

Abstract

Background and purpose: The discovery of chemical substances with carcinogenic properties has allowed the development of several experimental models of colorectal cancer (CRC). Classically, experimental models of CRC in mice have been evaluated through clinical or serial euthanasia. The present study aims to investigate the role of low endoscopy in the analysis of carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Methods: Thirty C57BL6 mice were divided into two groups: a control group with fifteen animals that underwent rectal instillation of saline solution on day 0 and a carcinogen group with fifteen animals that underwent a 100 mg/kg MNNG rectal instillation on day 0. In both groups, low endoscopies were performed on weeks 4 and 8. We used a validated endoscopic scoring system to evaluate the severity of colitis and colorectal tumor. Euthanasia was carried out at week 12. Results: We observed higher inflammation scores (p <0.001) and a higher number of tumors (p <0.05) in the MNNG group than the control group, both at weeks 4 and 8. A worsening of inflammation scores from the first to the second endoscopy was also noticeable in the MNNG group. There were no bowel perforations related to the procedure, and there was one death in the control group. Conclusion: Low endoscopy in experimental animals allows safe macroscopic evaluation of colorectal carcinogenesis without the need for euthanasia.

Keywords: colorectal carcinogenesis; experimental model.; low endoscopy.

MeSH terms

  • Administration, Rectal
  • Animals
  • Carcinogenesis / chemically induced
  • Carcinogenesis / pathology
  • Colonoscopy / methods
  • Female
  • Humans
  • Methylnitronitrosoguanidine / administration & dosage
  • Methylnitronitrosoguanidine / toxicity*
  • Mice
  • Neoplasms, Experimental / chemically induced*
  • Neoplasms, Experimental / diagnosis
  • Neoplasms, Experimental / pathology
  • Rectal Neoplasms / chemically induced*
  • Rectal Neoplasms / diagnosis
  • Rectal Neoplasms / pathology
  • Rectum / diagnostic imaging
  • Rectum / drug effects
  • Rectum / pathology

Substances

  • Methylnitronitrosoguanidine