수종 항암제(Bleomycin, 5-fluorouracil, ICRF-159 및 methotrexate)가 흰쥐의 간-취외분비선에 미치는 영향

Abstract

[한글]

Effect of Several Antitumor Agents on Pancreatico-Biliary Function in Rats

Yorng Man Choi

Department of Medical Science, The Graduate School, Yonsei University

(Directed by Professors: Sa Suk Hong and Choon Kyu Kim)

It clinical practice, antitumor 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 antitumorous activity is based on the inhibition of mitosis by

interference of synthesis of desoxyribonucleic acid (DNA) and ribonucleic acid

(RNA). However, the inhibition is nonspecific and involves not only cancer cell but

normal cell which grows rapidly. There are many experimental studies on

cytotoxicity but only a few on functional aspects by antitumor agents. Present

investigation is designed to study the effect of several antitumor 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 (1ml/100gm)

Group 2: Bleomycin treated (30mg/kg), consisted of 15 rats.

Group 3: 5-Fluorouracil (FU) treated (60∼160mg/kg), consisted of 45 rats.

Group 4: ICRF-159 treated (210-300mg/kg), consisted of 45 rats.

Group 5: Methotrexate treated (2.1∼3.0mg/kg), consisted of 30 rats.

The antitumor agents were injected i.p. every other day in divided dose for one

week.

The rats were anesthetized with secobarbital sodium (30mg/kg) and a fine

polyethylene catheter was inserted into 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

hematoxylin eosin stain.

The results obtained are summarized as follows:

1. The growth of rats treated with antitumor 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 groups increased at 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 methotrexate 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.

[영문]

It clinical practice, antitumor 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 antitumorous activity is based on the inhibition of mitosis by interference of synthesis of desoxyribonucleic acid (DNA) and ribonucleic acid

(RNA). However, the inhibition is nonspecific and involves not only cancer cell but normal cell which grows rapidly. There are many experimental studies on cytotoxicity but only a few on functional aspects by antitumor agents. Present investigation is designed to study the effect of several antitumor 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 (1ml/100gm)

Group 2: Bleomycin treated (30mg/kg), consisted of 15 rats.

Group 3: 5-Fluorouracil (FU) treated (60∼160mg/kg), consisted of 45 rats.

Group 4: ICRF-159 treated (210-300mg/kg), consisted of 45 rats.

Group 5: Methotrexate treated (2.1∼3.0mg/kg), consisted of 30 rats.

The antitumor agents were injected i.p. every other day in divided dose for one week.

The rats were anesthetized with secobarbital sodium (30mg/kg) and a fine polyethylene catheter was inserted into 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 hematoxylin eosin stain.

The results obtained are summarized as follows:

1. The growth of rats treated with antitumor 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 groups increased at 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 methotrexate 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.