DYNAMIC HISTOLOGY OF A RAT HEPATOMA AND THE RESPONSE TO 5-FLUOROURACIL

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Abstract
The cellular response of the rat hepatoma 3924A to a single i.p. injection of 5-fluorouracil was measured in respect of the spatial relationship of the cells to the tumor microvasculature. In this tumor the parenchyma is arranged in cords approximately 150 .mu.m thick around central capillaries. For untreated tumors, those cells at distances less than 80 .mu.m from the capillary had a mean [3H]TdR [thymidine] labeling index of 39% and a mitotic index of 2.1%; for those cells more than 80 .mu.m away, the values were 14 and 0.8%, respectively. Two days after 150 mg/kg of 5-fluorouracil, mean cord thickness was reduced by 25% and did not recover to the control level until 11 days after treatment. This was also true for the mitotic index. Recovery of the labeling index was complete 2 days earlier. Although absolute values of parameters were different in the populations adjacent to and remote from the capillary, the time course of recovery was similar, with a growth spurt 7-9 days after treatment. The results from this histologically-based assay were compared with those from biochemical/biophysical assays that sample the overall tumor population.