Toxicities and therapeutic effect of 5-fluorouracil controlled release implant on tumor-bearing rats.
OBJECTIVE
To investigate the toxicities, biodistribution and anticancer effect of 5-fluorouracil controlled release implant (5-FUCI) on Walker 256 carcinosarcoma cells in Wistar rats.


METHODS
Experiment 1: Wistar rats were randomly divided into three groups (27 rats per group). Blank implant was implanted in left lobe of the liver, and rats were treated with saline solution (in group A) or 5-fluorouracil (subcutaneous injection, group B). 5-FUCI was inserted in left lobe of the liver (group C). The gastrointestinal and hematological toxicities were observed and contents of element F in group C were assayed. Experiment 2: on day 6 after Walker-256 carcinosarcoma transplantation in left lobe of the liver, 5-FUCI was implanted in right lobe of the liver (group E) or left lobe (group F), and rats in control group (group D) were inserted blank implant. Tumor inhibition rate and survival time were investigated.


RESULTS
5-FUCI showed no obvious toxic effect, extraction of Evan's blue from gastrointestinal tissue was normal, the peripheral white blood cells and bone marrow nucleated cells were not reduced, compared with control group (P>0.05). Histological examination revealed that there were no visible changes in small intestinal mucosa, The concentration of 5-fluorouracil in left lobe of the liver was 9.84, 28, 34 times as much as those of right lobe of the liver, heart and kidney respectively after the implantation in group C. They kept a high level of fluorouracil in left lobe of the liver, ranging from (4.414+/-0.482) % to (7.800+/-0.804) %, for eight weeks. Survival days were 28.0+/-2.2, 30.0+/-3.2 and 38.7+/-6.7 d in group D, E and F, respectively.


CONCLUSIONS
5-FUCI shows no obvious toxicities to gastrointestinal tract and myelotoxicity. After implantation, it kept a high level of 5- fluorouracil in surrounding tissues of the implant for eight weeks. Its antitumor effect on Walker-256 carcinosarcoma is demonstrated.
He
Yin-Cheng
YC
Department of General Surgery, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, China. w030508h@public.wh.hb.cn
Chen
Ji-Wei
JW
Cao
Jun
J
Pan
Ding-Yu
DY
Qiao
Jian-Guo
JG
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002296:Carcinosarcoma / Q000473:pathology*; D003692:Delayed-Action Preparations; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D009368:Neoplasm Transplantation; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D000964:Antimetabolites, Antineoplastic; D003692:Delayed-Action Preparations; D005472:Fluorouracil