[Effect of 5-fluorouracil on DNA synthesis, mitotic index and spleen cells in mice after syngeneic bone marrow transplantation]. / Wplyw 5-fluorouracylu na synteze, DNA, indeks mitotyczny i sklad komórkowy w sledzionach myszy po syngenicznych przeszczepach szpiku.

The effects of 5-fluorouracil (5-FU) on DNA synthesis, mitotic index and cell composition of mouse spleens after 6 Gy X rays irradiation of mice and syngenic bone marrow transplantation were investigated. One dose of 5-FU (100 mg/kg body weight) administered 16 hrs after bone marrow transplantation reduced mitotic index and development of bone marrow grafts, but did not inhibit incorporation of 3H-thymidine into DNA. It correlates with high thymidylate synthase activity previously noted in the same model. Also the increased number of cells from lineage of erythroblasts correlates with high DNA synthesis and thymidylate synthase activity indicating, probably, the presence in those cell lines, the cells with high thymidylate synthase content, resistant to 5-FU.

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.