Effects of 5-fluorouracil on the cell kinetic and growth parameters of hepatoma 3924A

Abstract

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.

Response kinetics of host and experimental solid tumour after adriamycin

“…The rate of DNA synthesis was also elevated on Day 2 but depressed from Day 4 until Day 16. The elevation of both the DNA specific activity and labelling index on Day 2 suggests a redistribution of cells within the cell cycle, with an increased proportion of cells in the "S" period, as occurs with FU (Kovacs et al, 1975). The depression of both DNA specific activity and labelling indices between Day 4 and Day 16 could be the result of the direct effects of Adr on DNA synthesis, as well as a reduction of S-phase cells.…”

“…Clarkson and Humphrey (1977) reported that Chinese hamster ovary cells treated in mid-S phase showed a dose-dependent progression delay which was also reflected in the rates of DNA replication in the subsequent S phase. For hepatoma 3924A, the percentage of labelled cells remain high up to 1 week after FU administration (Kovacs et al, 1975 (Hopkins and Looney, 1978). The total tibial DNA content has been used as an index of marrow reserve.…”

“…THE kinetics of recovery for tumour and host organs after treatment with 5-fluorouracil (FU) have recently been determined for the experimental solid-tumour system, hepatoma 3924A (Kovacs et al, 1975;Hopkins et al, 1976;Looney et al, 1976) and these data have been used in the design of an effective chemotherapyradiotherapy combination for this tumour . The present report summarizes data obtained for hepatoma 3924A and its host the ACI rat after treatment with adriamycin (Adr), a relatively new chemotherapeutic agent which is effective against a wide range of human neoplasms (Carter, 1975).…”

Solid tumor models for the assessment of different treatment modalities: systematics of response to radiotherapy and chemotherapy.

“…Changes in tumor growth curves are one of the basic and sometimes the only means of evaluation of tumors as well as their response to treatment (10)(11)(12)(13)(14)(15). The subject of this report is a continuing search for more critical analytical methods for evaluating tumor growth.…”

Solid tumour models for the assessment of different treatment modalities: IV. the combined effects of radiation and 5-fluorouracil

“…However, one possible explanation for this synergistic effect is that the first agent produces a partial synchrony, increasing the number of cells in the more sensitive stages of the cell cycle when the second agent is given. Results from studies with the solid tumour model hepatoma 3924A have shown that there is a two-to-threefold increase in tumour-cell synchrony following radiation or FU, with the maximum increase occurring 12 h after single exposure to radiation and 24 h after FU in this solid tumour (Kovacs et al, 1975, 1 976a The results indicate that a series of combined FU and radiation doses given at 11-day intervals should in principle result in progressively smaller tumour volumes until the tumour is eradicated Hopkins et at., 1976;Kovacs et al, 1975Kovacs et al, , 1976aKovacs, Evans and Wakefield, 1976b). This therapeutic protocol now being tested would essentially transform the situation from an untreatable to a treatable one as neither the radiation dose alone (375-1500 rad) nor the FU dose alone (50-120 mg/kg) controls tumour growth.…”