Cellular kinetics and histological changes in experimental cancer of the uterine cervix

Carcinoma of the mouse uterine cervix was induced by the insertion of 20-methylcholanthrene (MC) thread into the uterine cavity. Through biweekly observations, it was seen that the histopathological carcinogenesis in the cervix was characterized by three distinct changes: normal epithelium, anaplastic epithelium, and carcinoma. The incidence rate of normal epithelium declined sharply in the first 4 weeks, followed by slight decline up to the 20th week of observation. Nevertheless, about 20% of MC-treated mice maintained histologically normal epithelium even at the 20th week. In contrast, the incidence rate of anaplastic epithelium increased sharply in the first 4 weeks and thereafter tended to decline. Carcinoma was first observed at the 4th week, and its incidence rate increased thereafter almost linearly, reaching about 50% of the MC-treated mice at the 20th week. Carcinoma was divided into two groups, the early invasive and the frank invasive types. The former was further subgrouped into epithelial bud, nodular growth, epithelial cord, and mixed type by the mode of stromal invasion. Studies using [3H]thymidine autoradiography on the cell proliferation kinetics in the process of carcinoma development showed that a labeling index became higher as the malignant changes of the epithelium advanced. Moreover, S-phase prolongation was observed with the malignant changes, and the cell cycle time did not differ markedly among normal epithelium (22.8 hr), anaplastic epithelium (23.0 hr), and frank invasive carcinoma (26.1 hr). However, the growth fraction was greatly varied; it was 28% for normal epithelium, 61% for anaplastic epithelium, 100% for early invasive carcinoma, and 100% for frank invasive carcinoma. These results indicate that the growth fraction increases as the malignant changes in the MC-treated mouse uterine cervix.