Cellular kinetics of invasive squamous carcinoma of the human cervix.

Abstract

The cell kinetics of two solid human tumors, invasive squamous carcinomas of the cervix, were studied by parenteral administration of tritiated thymidine followed by serial biopsy of the tumors at intervals for 24 hours, and subsequent radio-autographic analysis for mean grain counts and percent labeled mitoses at these times. In these two tumors, the majority of labeled cells were at the periphery of the tumor nodules (growth fraction of 41–53 percent). Tumor nodules appeared to grow by expansion from within, as newly formed cells migrated toward the centers of nodules. A significant proportion of interior cells (growth fraction of 17–20%) retained the capacity to divide, a function lost in the differentiation of normal epithelial cells, and thus were able to contribute to the total proliferative pool. Cell cycle times were 15.5 and 14.3 hours, and DNA synthesis times were 11.8 and 9 hours. These times are not unlike those of normal mammalian cells, adding to the evidence that rapid tumor growth is not necessarily dependent upon rapid cell proliferation. The observations that in these tumors: ( a ) the majority of dividing cells were at the periphery of nodules, ( b ) the growth fraction was reduced, i.e., maximum of 53 rather than 100 percent of basal cells were capable of dividing, and ( c ) periods of DNA synthesis were fairly long, points up the potential errors in estimating the cell cycle time from in vitro labeling studies. The possibility that cells in the interior of tumor nodules may be arrested in mitosis is described, a factor which may prevent even faster growth than is already observed.