Dynamic histology of a rat hepatoma and the response to 5-fluorouracil

The cellular response of the rat hepatoma 3924A to a single intraperitoneal injection of 5-fluorouracil has been measured in respect of the spatial relationship of the cells to the tumour microvasculature. In this tumour the parenchyma is arranged in cords approximately 150 micron thick around central capillaries. For untreated tumours, those cells at distance less than 80 micron from the capillary had a mean [3HTdR labelling index of 39% and a mitotic index of 2.1%, while for those cells more than 80 micron 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 labelling 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 spur' 7 to 9 days after treatment. The results from this histologically-based assay have been compared with those from biochemical/biophysical assays that sample the overall tumour population.