Tumour cords have been examined quantitatively in two rat hepatomas, 3924A and H-4-II-E, that differ in their radiobiological oxygenation status (oxygen enhancement ratio for growth delay [tumour clamped: tumor 'in air'] was 1.35 for 3924A and only 1.08 for H-4-II-E). The average thickness of tumour cords in 3924A was 118 microns and only 69 microns in H-4-II-E. The migration rates across the cords of the two tumours were approximately the same (1.7 and 1.4 micron X h-1) but for any given distance from the subtending blood vessel, the proportion of histologically-dead cells within the cord was always higher for H-4-II-E. Volume for volume, H-4-II-E contained four times as much vascular space as 3924A but it is suggested that the poor quality of this vasculature in H-4-II-E contributed to its relative radioresistance.

Intact rats trained on a controlled feeding and lighting schedule designated ;8+16' exhibited diurnal oscillations in liver weight, glucokinase activity and liver glycogen content. Glucokinase activity expressed as units/g of liver decreased to 30% of that from unoperated controls during the first 48h after partial hepatectomy and returned to near normal values in 2 weeks. When the glucokinase activity was expressed as units/liver per 100g body wt., a decrease to 50% of control activity was observed between 24 and 48h after the operation. A similar pattern was found for pyruvate kinase type I. In contrast, pyruvate kinase type III activity increased after partial hepatectomy. It is suggested that the newly divided cells after partial hepatectomy do not synthesize glucokinase and pyruvate kinase I but do synthesize pyruvate kinase III. Glycogen was found to accumulate as early as 24h after partial hepatectomy, and normal concentrations were reached after 48h if the operation was performed at times other than during the feeding periods.

No abstract

A computer program has been developed to quantitatively evaluate changes in tumor growth rates of a solid tumor model (hepatoma 3924A) after a series of radiation doses from 375 R to 3750 R. The computer-derived growth curves are simulated from the volumes of the individual tumors rather than from the mean tumor volume at any specific time point after treatment. The ability to generate ata from a family of tumor growth curves permits a more precise evaluation of therapeutic effects on tumors than can beobtained with conventional methods. The quantitative determination of equivalent amounts of radiation needed to produce comparable 5-fluorouracil-induced changes in tumor growth rate has been made. The ability to determine quantitatively radiotherapeutic and chemotherapy equivalents on these solid tumor models has direct implications in regard to our effort to improve the treatment of cancer. At present no specific solid tumor or groups of solid tumors have provided al1 of the necessary information for clinical utilization in therapeutic scheduling of different forms of cancer treatment. Since solid tumors comprise the majority of human cancer, one of the primary objectives of these studies has been the establishment of a solid tumor model that could serve both as a system for devising improved therapeutic scheduling and for a better understanding of solid tumors. The rate of change of tumor volume with time is one of the basic measurements for the study of tumor growth (1-9).While Morris hepatomas have been extensively used in cancer research, no systematic study has been made of the effects of radiation on these solid tumors (10,11). This study of the effects of different x-radiation doses on tumors is part of a continuing study of the assessment of therapeutic response of different modalities of treatment in this experimental solid tumor system. Studies of the effects of radiation on cycle times, potential doubling times, cell loss factor, and the fraction of proliferating and nonproliferating cells (growth fraction) are needed along with the effects of radiation on tumor growth rates to assess treatment properly. This report is primarily concerned with the methods of evaluation of radiation-induced changes in tumor volumes and the results of different doses of radiation over a range of 375-3750 R.MATERIALS AND METHODS Female ACI rats were inoculated subcutaneously in the back with 3924A hepatoma cells by Dr. Harold Morris in Washington D.C. and shipped to this laboratory. The rats were maintained under standard laboratory conditions including commercial laboratory rat chow (Charles River Laboratories, Wilmington, Mass.) supplied ad libitum, and a 12 hr lighting schedule, the dark period beginning at 8:00 p.m.Tumor volumes, V, (mm3) were calculated from measurements of length (L), width (W), and height (H) (5). It was assumed that the tumors are approximately hemiellipsoids whose volume is lit L-W-H (1). The tumors were measured and the rats weighed daily before radiation and for 6 days afterward. The m...

Summary.-The effect of 5-fluorouracil (5-FU) on the growth and cellular proliferation of hepatoma 3924A was studied using the following parameters as indices of tumour response: (1) volume measurements, (2) cell kinetic analysis including estimates of both growth and cell loss fractions, (3) changes in tumour histology and (4) tumour DNA content and DNA synthesis. Of a series of single intraperitoneally injected doses (25-300 mg/kg body weight), 150 mg/kg interrupted tumour growth most effectively with minimal toxicity within 168 h, and after 10 days treated tumour volumes were only 42% of untreated tumour size. Doses of 25 mg/kg failed to change the rate of growth while 300 mg/kg exceeded the LD50.