[TS inhibition rate and flow cytometric analysis of DNA content in preoperative chemotherapy with biochemical...

Investigation of the TS (Thymidylate Synthetase) inhibition rate and flow cytometric studies of DNA content were conducted in 20 patients with human colorectal cancer who had undergone preoperative chemotherapy. Preoperative regimens of HCFU 240 mg/m2/day, given by 14-day oral dosage or HCFU 240 mg/m2/day and DP (Dipyridamole) 300 mg/body/day, both 14-day oral dosage were used. In 10 patients undergoing preoperative treatment with only HCFU and 10 patients with preoperative treatment of HCFU and DP, the free and total TS activities were measured with the tumor tissue and intact mucosa obtained from surgically resected tissues. With the TS activity, the TS inhibition rate (TSIR) was calculated from the free and total TS activities. Flow cytometric analysis of DNA content was measured before and after operation, and the difference was investigated. The changes of DNA histogram were found postoperatively in 2/10 (20%) patients with the HCFU dosage, and in 4/10 (40%) with the HCFU+DP dosage. TSIR exceeded 50% in all of these patients. The TSIR with DP (average, 64.5%) was higher than that of without DP (average, 57.5%) among them. Histological changes were found in 6/20 (30%) patients with preoperative chemotherapy. In all patients with preoperative chemotherapy, TSIR with DP (average, 63%) was higher than that without DP (average, 33%), but TSIR of normal tissue (average, 25%) was lower than that of these tumor tissues. These results showed that the benefit of this chemotherapy, including the change of DNA histogram, was especially higher when the TSIR of tumor tissue was high, and the TSIR with DP was also high.