Increased azidodeoxythymidine metabolism in the presence of fluorouracil reflects increased thymidine kinase activity Meeting abstract).

Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.

Increased azidodeoxythymidine metabolism in the presence of fluorouracil reflects increased thymidine kinase activity Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 34:A1799 1993. Unique Identifier : AIDSLINE MED/93692740
Darnowski JW; Goulette FA; Dept. of Medicine, Brown Univ. and Roger Williams Hosp., Providence,; RI 02908

Abstract: Incubating the human colon tumor line HCT8 in media containing 5 uM fluorouracil (FUra) + 5 uM [3H] azidothymidine (AZT) for 24 hr results in cellular AZTMP pools of approx 280 pmol/10(6) cells, 10-fold more than observed after incubation in 5 uM AZT alone. To evaluate this phenomenon, we quantitated the activity of the proximal enzymes of AZTMP metabolism in cells incubated for 24 hr in media with 5 uM FUra. 5'-Nucleotidase activity was unchanged following FUra. In contrast, the activity of thymidine kinase TK, 108 nmol/hr/mg prot) and thymidylate kinase (dTMPK, 552 nmol/hr/mg prot) were 40% and 5-fold, respectively, above controls. Since AZTMP is a poor substrate for dTMPK, this modest increase in TK appears responsible for the enormous increase in AZTMP pools observed. Studies of the relationship between this effect and TS activity are proceeding.

Keywords: *Fluorouracil/PHARMACOLOGY *Zidovudine/ANALOGS & DERIVATIVES
931130
M93B5842

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