Genesis of 1,2-dimethylhydrazine-induced colon cancer. A light and electron microscopic study

Rats treated with 1,2-dimethylhydrazine (DMH) exhibited colonic mucosal dysplastic foci prior to the development of tumors. Ultrastructurally, these, as well as the cancers that subsequently developed, were characterized by alterations in plasma membranes and an increase in cytoplasmic ribosomal particles, principally in stem cells and their absorptive derivatives. Rare Kulchitsky cells appeared preserved, but the mucin-producing or goblet-cell elements were compressed and atrophic. In addition, nuclear aberrations were more pronounced in the cancer than in the dysplastic foci. The principal ultrastructural difference between the so-called well-differentiated and mucinous forms of DMH-induced cancers was the presence of frequent intracytoplasmic lumens in the mucinous form. Such structures represented the analogues of signet ring cells observed by light microscopy. This experimental model of human colonic cancer shows that the mucosal stem-cell and dysplastic lesions represent their cytogenetic and histogenetic progenitors.