The mode of growth and compartmentalization of neoplastic glands during experimental colon carcinogenesis

During the growth of 1,2-dimethylhydrazine (DMH)-induced colon neoplasms in mice from microscopic ones at 9 weeks to macroscopic, invasive ones at 25-26 weeks after the initiation of DMH treatments, the neoplastic glands became increasingly but variably elongated and tortuous, with epithelial evaginations and/or invaginations. For assessment of the mode of growth and genesis of heterogeneity of neoplasms, colon neoplasms induced by two different cumulative doses of DMH were compared at 25-26 weeks after the initial DMH injection. At this time they invaded the colonic wall similarly in depth. However, neoplasms that developed in mice given a higher cumulative dose of DMH had a more homogeneous cell population, a higher proliferative activity, and more apoptotic bodies than those with a lower dose. By 73 hours after multiple tritiated thymidine injections, most neoplastic cells became labeled. There were numerous foci of unlabeled cells seen among, or alternating with, areas of labeled cells. Epithelial evaginations into the glandular lumen consisted of proliferating cells and/or differentiated cells; whereas invaginations into the lamina propria contained only proliferating cells. These findings suggest a compartmentalization of neoplastic glands into multiple neoplastic clonogenic units during growth, from which cellular heterogeneity and architectural complexities of neoplastic glands develop.