Panfil B
Acta Pol Pharm. 1989;46(2):195-9.
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.
研究了5-氟尿嘧啶(5-FU)对接受从未经处理小鼠、经苯肼处理小鼠或经苯肼和5-FU处理小鼠采集的骨髓移植的受体小鼠脾脏中胸苷酸合成酶活性及骨髓组织发育的影响。一剂5-FU(100mg/kg体重)可减少所有供体骨髓移植的发育。无论是否进行骨髓移植,照射后前三天胸苷酸合成酶的活性急剧下降。接下来,在连续3天里,未处理和经5-FU处理的小鼠体内该酶的活性均急剧增加。在接受对照骨髓移植并随后用5-FU处理的小鼠脾脏中发现了最高的胸苷酸合成酶活性。尽管脾脏重量进一步减轻,但仍出现了高酶活性。因此,5-FU完全阻止了脾脏中骨髓移植的发育,但却以一种自相矛盾的方式增加了胸苷酸合成酶的活性。从经苯肼和5-FU诱导该酶处于高产状态时采集的骨髓发育而来的骨髓组织中的胸苷酸合成酶,对5-FU并未表现出抗性增加。