[Experimental study on the clonogenic assay--in vitro and in vivo chemosensitivity tests of human tumor xenografts serially transplanted into nude mice].

In order to determine the optimal conditions of the clonogenic assay for predicting antitumor activity in vivo, experimental chemosensitivity tests in vitro and in vivo were performed using a human gastric carcinoma strain, H-111 serially transplanted into nude mice. According to the method of Salmon and Hamburger, 5-fluorouracil (5-FU) was added to dissociated tumor cells at concentrations of 0.1, 1 and 10 micrograms/ml continuously for 2 weeks in the upper layer of a double agar preparation. The transplanted H-111 tumors in nude mice were treated with 30, 60 and 120 mg of 5-FU per kg. The antitumor activities were evaluated by the T/C ratio of the colonies in vitro and the T/C ratio of tumor weights in vivo. Pharmacokinetic analysis of 5-FU was conducted by bioassay with Staphylococcus aureus in the agar and in the serum of mice. When areas under the curves in vitro and in vivo were supposed to be equivalent, the antitumor activities of 5-FU in vitro and in vivo could be correlated quantitatively in terms of T/C ratios. The drug concentration in the clonogenic assay for predicting the effect of the MTD of 5-FU in vivo (50 mg/kg X 3) was calculated to be 1 microgram/ml for 2 weeks.