Effects of 5-fluorouracil on thymidylate synthase activity and development of bone marrow grafts in spleens of irradiated mice.
The effects of 5-fluorouracil (5-FU) on thymidylate synthase activity and development of myelopoietic tissue in spleens of recipient mice grafted with bone marrow collected from untreated mice, treated with phenylhydrazine or phenylhydrazine and 5-FU were investigated. One dose of 5-FU (100 mg/kg body weight) reduced development of bone marrow grafts from all donors. The activity of thymidylate synthase sharply declined during the first three days after irradiation irrespective of bone marrow transplantation. Next, during consecutive 3 days the activity of the enzyme sharply increased both in mice untreated and treated with 5-FU. The highest thymidylate synthase activity was found in spleens of mice grafted with control bone marrow and next treated with 5-FU. That high enzyme activity appeared in spite of further reduction of spleen weight. Thus, 5-FU prevented completely development of bone marrow grafts in spleens but increased thymidylate synthase activity in a paradoxical manner. Thymidylate synthase in myelopoietic tissue developed from bone marrow, collected in the state of hyperproduction of that enzyme induced with phenylhydrazine and 5-FU, did not show increased resistant to 5-FU.
Panfil
B
B
D000818:Animals; D016026:Bone Marrow Transplantation / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D005472:Fluorouracil / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011182:Postoperative Care; D013154:Spleen / Q000187:drug effects / Q000502:physiology / Q000601:surgery*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors; D016042:Transplantation, Heterotopic / Q000502:physiology*; D014916:Whole-Body Irradiation
D013940:Thymidylate Synthase; D005472:Fluorouracil