[Conversion of 5'-deoxy-5-fluorouridine to 5-FU by pyrimidine nucleoside phosphorylases in normal and tumor tissues from rodents bearing tumors and cancer patients].
Enzyme levels of pyrimidine nucleoside phosphorylase, which is an essential enzyme for the phosphorolysis of 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil (5-FU), in normal and tumor tissues were investigated. In all mouse strains tested, the enzyme level was found to be higher in the small intestine and stomach than other tissues, while in rats a higher level of the enzyme in the lung was also observed additionally. The enzyme levels of tumor tissues varied in tumor cell lines transplanted. P388 leukemia, Ehrlich ascites carcinoma, sarcoma 180, colon 26 carcinoma, and Lewis lung carcinoma cells contained high levels of the enzyme and the mice bearing these tumors responded well to the therapy with 5'-DFUR than its active metabolite 5-FU, while 5'-DFUR did not show clear advantage over 5-FU against L1210 or LSTRA leukemia, in which the enzyme levels were low. These results indicate that there is some correlation between the enzyme level and antitumor efficacy of 5'-DFUR. In human specimens, the enzyme levels were 2-6 times higher in tumors than those of the corresponding normal tissues and those adjacent to the tumors. These results predict that 5'-DFUR seemed to be converted efficiently to 5-FU also in human tumors.
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D002279:Carcinoma 256, Walker / Q000378:metabolism; D005467:Floxuridine / Q000378:metabolism*; D005472:Fluorouracil / Q000378:metabolism*; D006801:Humans; D007939:Leukemia L1210 / Q000378:metabolism; D007941:Leukemia P388 / Q000378:metabolism; D051379:Mice; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism*; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism*; D010430:Pentosyltransferases / Q000032:analysis / Q000502:physiology*; D057845:Pyrimidine Phosphorylases; D051381:Rats; D012510:Sarcoma 180 / Q000378:metabolism
D000970:Antineoplastic Agents; D005467:Floxuridine; D010430:Pentosyltransferases; D057845:Pyrimidine Phosphorylases; D005472:Fluorouracil; C025034:doxifluridine