Hopkins H A, Kovacs C J, Looney W B, Wakefield J A
Cancer Biochem Biophys. 1976;1(6):303-12.
Time relationships for recovery of several host organs from toxic effects of 5-fluorouracil were determined in ACI rats bearing Morris hepatoma 3924A. A single injection of 150 mg/kg body weight 5-fluorouracil (the LD10) resulted in loss of 90% of the tibial bone marrow, 60% of the intestinal mucosa, and 90% of the thymus as measured by total DNA content of the organs. Organ DNA contents following 150 mg/kg of the drug were minimal on day 3 for intestine and on day 5 for marrow and thymus. A return to pretreatment or higher levels of DNA was observed by day 4 for intestine, day 11 for tibial marrow, and day 19 for thymus. Incorporation of 3H-deoxyuridine into host organ DNA after 150 mg/kg 5-fluorouracil was inhibited 36 hrs for intestine, 3 days for thymus, and 5 days for tibial bone marrow. Inhibition of 3H-deoxyuridine incorporation into DNA was similar for 50, 100, and 150 mg/kg doses both in tumor and in host organs, but recovery of 3H-deoxyuridine incorporation and DNA content of host organs began later with the higher doses of 5-fluorouracil. Maximal incorporation of 3H-deoxyuridine into DNA was observed on day 4 for intestine, day 8 for marrow, and day 9 for thymus after treatment with 150 mg/kg 5-fluorouracil. Animal lethality following the second of two 150 mg/kg injections of 5-fluorouracil was related to the extent of recovery of intestinal mucosa and bone marrow at the time of the second injection. Survival decreased to 0% for normal rats when the interval between injections was 3-4 days, improved at 5 days and was 100% when the interval was 10-11 days.
在携带Morris肝癌3924A的ACI大鼠中，测定了几种宿主器官从5-氟尿嘧啶毒性作用中恢复的时间关系。单次注射150mg/kg体重的5-氟尿嘧啶（LD10），通过器官总DNA含量测定，导致胫骨骨髓损失90%、肠粘膜损失60%、胸腺损失90%。给予150mg/kg该药物后，肠的器官DNA含量在第3天最低，骨髓和胸腺在第5天最低。到第4天肠、第11天胫骨骨髓、第19天胸腺观察到DNA恢复到预处理水平或更高水平。给予150mg/kg 5-氟尿嘧啶后，3H-脱氧尿苷掺入宿主器官DNA的情况在肠中被抑制36小时，在胸腺中被抑制3天，在胫骨骨髓中被抑制5天。50、100和150mg/kg剂量的5-氟尿嘧啶对肿瘤和宿主器官中3H-脱氧尿苷掺入DNA的抑制作用相似，但随着5-氟尿嘧啶剂量增加，宿主器官中3H-脱氧尿苷掺入和DNA含量的恢复开始时间延迟。给予150mg/kg 5-氟尿嘧啶治疗后，肠在第4天、骨髓在第8天、胸腺在第9天观察到3H-脱氧尿苷掺入DNA的最大值。两次150mg/kg注射5-氟尿嘧啶中的第二次注射后动物的致死率与第二次注射时肠粘膜和骨髓的恢复程度有关。当注射间隔为3-4天时，正常大鼠的存活率降至0%，在第5天时有所改善，当间隔为10-11天时存活率为100%。
