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KMID : 0371319740160070001
Journal of the Korean Surgical Society
1974 Volume.16 No. 7 p.1 ~ p.12
Effect of Several Antitumor Agents on Pancreatico-Biliary Function in Rats

Abstract
In clinical practice, anti tumor agents-have been widely used in the treatment- of disseminated cancer. Recently, the agents are being used for the treatment by regional perfusion or-in purpose of obtaining shrinkage of a large tumor to enable to operate surgically. Furthermore, it is an adjuvant therapy in cancer surgery to prevent spreading of -the tumor cell and to destroy possible residual lesion. The mechanism of antitumor activity is based on the inhibition of mitosis by interference of synthesis of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). However, the inhibition is nonspecific and involves not only cancer cell but also normal cell, which grow rapidly. There are many experimental studies on cytotoxicity but only a few¢¥ on functional aspects by anti tumor agents. Present investigation is designed to study the effect of several anti tumor agents on pancreatico-biliary function in rats.
One hundred and sixty five male albino rats weighing 150 gm around were divided into five groups as follows;
Group 1: Control group consisted of 30 rats, treated with saline (1 ml/100 gm)
Group 2: Bleomycin treated (30 mg/kg), consisted of 15 rats.
Group 3: 5-Fluorouracil (FU) treated (60~160 mg/kg), consisted of 45 rats.
Group 4: ICRF-159 treated (210~300 mg/kg), consisted of 45 rats.
Group 5: Methotrexate treated (2.1~3.0 mg/kg), consisted of 30 rats.
The anti tumor agents were injected i.p. Every other day in divided dose for one week.
The rats were anesthetized with secobarbital sodium (30 mg/kg) and a fine polyeehylene catheter was inserted in to pancreatico-biliary duct and collected the juice for two hours. Blood sampling was done from abdominal aorta for determination of serum amylase and protein. Amylase activity was expressed as much as maltose liberated from a starch substrates. The maltose was determined by method of Nelson. Lipase activity was measured by modified Cherry and Crandall method. Liver and pancreas were fixed in 10% formalin and prepared histologic section with hematoxylineosin stain.
The results obtained are summarized as follows.
1. The growth of rats treated with anti tumor agents for a week course was slightly inhibited and the mortality during the course was seen in groups treated with methotrexate, 5-fluorouracil and ICRF-159 in decreasing order. No death was observed in bleomycin or control group.
2. In all groups except bleomycin, weight of testis was increased by the antitumor agents and decreased thereafter. In bleomycin, the weight was decreased by treatment and returned to control level after cessation. The weight of spleen in all agroups increasedal 1 week after cessation of the treatment and it is particularly significant in methotrexate group.
3. Serum protein value was increased in both FU and methotrexate groups and returned to control level at one week after cessation. Serum amylase level was significantly increased only in methotrexate group; however, the other groups showed rather decreased levels.
4. Pancreatico-biliary secretion was increased in all groups treated with antitumor agents for a week course and showed an elevated level until 2 weeks after cessation. Amylase content in math-otrexate group was significantly decreased and lipase was increased particularly in both FU and methotrexate groups, however, the levels were returned to control value at one and two weeks after cessation, respectively.
By these findings it is recognized that pancreatico-biliary exocrine function as well as histology were considerably changed by a week course of the antitumor agents, however, in contrast to FU or methotrexate, the toxicity of the new agents, bleomycin and ICRF-159, were far less.
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