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항대사제(抗代謝劑)가 백서간세포 미세구조(白鼠肝細胞微細構造)에 미치는 영향에 관한 연구

Other Titles
 Ultrastructural changes of rat liver cells induced by metabolic inhibitors (Ethionine, methotrexate, endoxan, a 
Authors
 김기수 
Issue Date
1970
Description
의학과/박사
Abstract
[한글]

[영문]

The mechanisms of action of antimetabolites used for the chemotheraphy of cancers have been well established, and are known to be different from each other. Most of these antimetabolites act as inhibitors of nucleic acid synthesis, although the site of inhibition or block is different according to the type of antimetabolites (Heiderberger et at., 1957; Rick et al., 1958; Werkheiser, 1963; Bertino et al., 1964). Consequently they eventually result in inhibition of protein synthesis

The ultrastructural alterations of the lifer cell fellowing treatment with various agents are currently being studied in correlation with biochemical analysis. Thus some of the morphologic alterations have been explained on the basis

of biochemical alterations. However, many of ultrastructural changes appear to be a common Phenomenon doe to divergent causes Therefore it would be a worthwhile effort to elucidate further the basis or mechanisms of many morphologic alterations which knave not been well explained.

The present study is to investigate talc ultrastructural alterations of the rat liver cell fellowing the administration of several antimetabolites of known action and to observe, if there is any specific type of change to ascribe to the different mode of action.

Albino rats weighing around 200 gms were used for the experiment, and the antimetabolites comprised of ethionine, methotrexate, endoxan, and 5-fluorouracil. The animals were divided into five groups and treated as followings.

Group Ⅰ : Normal untreated control (27 animals).

Group Ⅱ : Ethionine injected group (27 animals).

Group Ⅲ : Methotrexate injected group (27 animals).

Group Ⅳ : Endoxan injected group (27 animals).

Group Ⅴ : 5-fluorouracil injected group (27 animals).

Normal control animals were given 1.0 ml of normal saline injection intraperitoneally. Ethionine was given by a single intraperitoneal injection in a dose of 1 mg per gm of animal body weight dissolved in distilled water.

Methotrexate, endoxan, and 5-fluorouracil were also given by a single intraperitoneal injection in a dose of 3 mg, 100 mg, and 200 mg Per kg of body weight, respectively. At intervals of 6,12,18,24,36,48,72,96 hours, and 7days after talc injection of antimetabolites 3 animals from each group were killed, and

specimens for light and electron microscopic examinations were obtained immediately from the liver.

Specimens for the light microscopic examinations were fixed in 10% neutral formalin and embedded in paraffin. Sections about 6μ thick from talc paraffin block were stained with hematoxylin and eosin for overall histologic change, and methyl-green pyronin staining was used to examine alterations of cytoplasmic RNA.

Specimens for the electron microscopic examinations were cut in 1 cu. mm size and fixed in 1% osmic acid in vernal buffer of pH 7.4, fellowed by dehydration in graded al7771. They were embedded in Epon 812 and cut into 400 to 500 A thickness with glass knife. After staining with uranyl acetate and lead hydroxide, observation was made with Hitachi 11-E model electron microscope.

Methyl green pyronin staining revealed an abundant amount of pyronophilic granules forming clusters and network around the nuclei of liver cells in the control rats, However, pyronophilic materials decreased marke이y or were almost absent 6 hours after the injection of ethionine. It was also decreased moderately

in 6-fluorouracil treated animals, and very slightly in animals treated with endoxan. The animals treated with methotrexate also showed a alight decrease of pyronophilic substance in the liver cells, but not until 72 hours after the methotrexate injection. This time lapse is thought to be duct to a reserve of folic

acid in the liver cells formed before methotrexate injection.

The ultrastructural alterations consisted of disorganization, dilatation and detachment of ribosomes of rough endoplasmic reticulum; hyperplasia and dilatation of smooth endoplasmic reticulum; swelling of mitochondria; and accumulation of

lipids in the cytoplasm of liver cells. The degree of rough and smooth endoplasmic reticulum change was most marked in the animals treated with ethionine, and this appeared to be well correlated with talc decrease of pyronophilic substance by

methyl green pyronin staining. Thc swelling of mitochondria was most marked in the animals treated with methotrexate or endoian. The amount of lipid accumulation was most marked in ethioninc treated animals, fellowed by 5-fluorouracil treated group.

No lipid accumulation was noted in the animals treated with endoxan. The accumulation of lipid in ethionine treated group was preceded by appearance of dense bodied in the rough endoplasmic cisternae, but no such chance was noted in other groups.

Changes of nuclei and nucleoli consisted of enlargement of nuclear size, irregularity of nuclear membrane, increased numbers of nucleoli with increase of size and early microsegregation. These nuclear chances were almost absent in the animals treated with endoxan, and most marked in the animals treated with

ethionine, followed by animals treated with 5-fluorouracil.

In summary, the data obtained by the present stuffy indicate that most of the ultrastructural alterations of rat liver cells following the administration of antimetabolites known to have different modem of action are mostly similar in quality although some quantitative differences are noted. This was thought to be

due to a common biochemical end result, namely inhibition of nucleic acid synthesis and hence protein synthesis, although the blocking site of the chemical process is different in action in each agent.
Full Text
https://ymlib.yonsei.ac.kr/catalog/search/book-detail/?cid=CAT000000008273
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Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 3. Dissertation
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/125923
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