Corrupted colonic crypt fission in carcinogen-treated rats

BACKGROUND: The colonic crypts in rats reproduce themselves by symmetric fission at the base of the crypts, and proceeding upwards, generate two separate identical crypts. Recently we reported corrupted colonic crypt fission (CCCF) in rats with colonic carcinoma. Here we investigated whether CCCF also occurred in the colonic mucosa without carcinoma in carcinogen-treated rats. METHODS: Filed Swiss-roll sections from 35 male rats (25 treated with 1,2-dimethyhydrazine (DMH) suspended in EDTA solution, and 10 EDTA-treated) were reviewed. CCCF were regarded those with either asymmetric basal fission, asymmetric lateral sprouting/lateral fission, basal dilatations, or spatial aberrations of the normal (vertical) axis. RESULTS: 202 CCCF (38%) were recorded amongst 533 crypts with fission in DMH-treated rats, and only one CCCF (0.1%) was found amongst 571 crypts with fission in EDTA-treated rats (p<0.05). The basal aspect of four adenomas included in Swiss roll sections exhibited CCCF lined either with indigenous (non-dysplastic) epithelium or with dysplastic epithelium. CONCLUSION: It was demonstrated that CCCF without dysplasia develop in carcinogen-treated SD rats. As judged by the figures presented, the possibility that the epithelium in those corrupted crypts was successively replaced by top-down growing dysplastic cells, could not be totally rejected. This is the first report showing that non-dysplastic CCCF may antedate the very early stages of colonic carcinogenesis in SD rats.