[Dihydropyrimidine dehydrogenase and thymidylate synthase in colon carcinoma].
Dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) in cancer are considered to play key roles in the sensitivity to 5-FU-based chemotherapy. We measured DPD activities and TS content in cancer and normal mucosa obtained from 59 patients with colorectal carcinomas and examined their relationship and clinicipathological relevance. DPD activity was significantly decreased in cancer compared to that in adjacent mucosa, irrespective of the clinicopathological parameters (p < 0.0001), while TS content was significantly increased in cancer (p < 0.0001). DPD activity in cancer correlated with that of the normal mucosa (r = 0.57, p < 0.001), but no correlation was found between TS content of normal mucosa and cancer. The DPD activity difference between cancer and normal mucosa was significantly correlated with difference in TS content (r = 0.70, p < 0.0001). These results suggest that the reduction of DPD activity is associated with the elevation of TS content, which may be connected with the development of 5-FU resistance and the effectiveness of biochemical modulation through the stabilization of TS inhibition with folic acid in colon carcinoma.
Hamaji
Masayasu
M
Dept. of Surgery, Higashiosaka City General Hospital.
Nishida
Toshiroh
T
Miyazaki
Satoru
S
Nishida
Yukihiro
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000201:enzymology*; D042943:Dihydrouracil Dehydrogenase (NADP); D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D010088:Oxidoreductases / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000378:metabolism*
D010088:Oxidoreductases; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase