The effect of the carcinogen, 1,2-dimethylhydrazine, on turnover of 3H-thymidine labeled cells from mucosal glands of mouse colon

Abstract

1,2-dimethylhydrazine (DMH), administered weekly to mice for 20 weeks, induces tumors in the distal segment of colon. Tumors are preceded by enlargement of the mucosal glands resulting from increases in the number of total cells and 3H-thymidine labeled cells/crypt. Cells located in the crypt base normally undergo 2-3 division as they migrate toward the lumen, and they become post-mitotic in the upper crypt. It is not known if cells in these enlarged crypts have rates of turnover similar to cells in normal crypts. Groups of w/s female mice were treated with DMH (20 mg/kg body wt) for 3,8, or 16 weeks; controls were given 0.001 M EDTA. After treatment, the animals were injected with 3H-thymidine and killed one hour or 1,2,4,7 or 17 days later. Autoradiographs were prepared from sections of distal colon. The total cells/crypt column in 30 crypts/animals were counted. Crypts were divided into 10 equal segments based on the crypt length and the labeled cells/segment were counted. The relative number of labeled cells and the distribution of these cells within crypts were similar in DMH-treated and control animals after one hour. However, as the cells migrated toward the lumen, the number of labeled cells doubled after 2 days and tripled after 4 days in DMH-treated animals but only doubled during the 4 days in controls. This difference caused by retention of an increased number of dividing cells in the lower 4 segments of the crypts and suggests an increase in those cells that divide twice. In addition, increased numbers of labeled cells were retained in the upper 3 segments of DMH-treated animals after 4 days. These findings indicate that the crypt cells of DMH-treated animals are generally more immature than those of controls and this immaturity contributes to the enlargement of mucosal glands during carcinogenesis.