Premium
On the mechanism of cytotoxicity of fluorinated pyrimidines in four human colon adenocarcinoma xenografts maintained in immune‐deprived mice
Author(s) -
Houghton Janet A.,
Houghton Peter J.
Publication year - 1980
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19800315)45:5+<1159::aid-cncr2820451320>3.0.co;2-z
Subject(s) - cytotoxicity , immune system , dose , medicine , floxuridine , cancer research , pharmacology , rna , tumor cells , mechanism of action , chemotherapy , immunology , fluorouracil , biology , biochemistry , in vitro , gene
Abstract Three fluorinated pyrimidines, 5‐fluorouracil (FUra), 5‐fluorouridine (FUrd), and 5‐fluoro‐2′‐dexoyuridine (FdUrd), have been studied in four human colonic tumor xenograft lines. The preliminary findings may be summarized as follows: 1) after equimolar dosages, the agent reaching the highest concentration in the tumor produced the highest level of fluorodeoxyuridylate (FdUMP); 2) within a tumor line, the order of response to the three agents is related to the order of FdUMP‐generation; 3) the tumor‐response did not correspond to the level of analogue‐incorporation into RNA; 4) the measurement of levels of free FdUMP in tumors is a poor prognostic indicator of drug‐response; and 5) the levels of FdUMP in the tumors are maintained for considerable periods and appear to be dependent upon the maintenance of the levels of either FUra or FUrd, irrespective of the parent agent administered.