Differential Susceptibility of AKR, C57BL/6J, and CF1 Mice to 1,2-Dimethylhydrazine-Induced Colonic Tumor Formation Predicted by Proliferative Characteristics of Colonic Epithelial Cells23

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Abstract
The proliferative characteristics of the colonic mucosae of various mouse strains were examined to determine their value in forecasting the differential susceptibility of each to 1,2-dimethylhydrazine (DMH)-induced tumor formation. The control labeling index (LI) was highest (9.9±2.6) and the proliferative compartment (PC) widest in the DMH-sensitive CF1 strain, whereas the LI was lowest (7.3±1.3) (P>0.01) and the PC shortest in the AKR resistant strain. The size of the PC and the LI for moderately resistant C57BL/6J mice lay between these values (8.5±1.1). Pooled data from 1 week after the fifth and sixth injections and 12 weeks after the first injection of six showed elevated LI in the distal colons of all DMH-treated mice. Distribution analyses of [3H]thymidine-labeled cells indicated extension of the PC (Stage I abnormality) in all strains with a shift of DNA-synthesizing cells from the major zone or lower third to the middle and upper thirds of the crypt (Stage II abnormality) occurring primarily in the CF1 strain. Cytotoxicity measurements at 6 hours and compensatory DNA synthesis at 3 and 4 days after DMH injection (20 mg/kg body wt) revealed similar relative response levels in CF1 and AKR mice, which suggested induction initially of like numbers of mutations. Indigenous conditions shown to influence the expression of colonic neoplasia are the level of DNA synthesis and the dimensions of the PC within the mucosa.