Estrogen 투여 및 난소적출이 3-methylcholanthrene처치 백서자궁에 미치는 형태학적 연구

Abstract

[한글]

[영문]

In recent years many studies have been done to investigate the correlation between the genesis or growth of carcinoma of the uterus and the sex hormones; however, little has benn known of the effect of estrogen on the growth of neoplasm, especially on the growth of uterine tumor.

Many investigators have induced the precancerous lesion and the carcinoma of uterine cervix in experimental animals (Loeb, et al., 1936: Suntzeff et al., 1938; Gardner, et at., 1938; Allen and Gardner, 1941), and also induced squamous metaplasia and endometrial hyperplasia in experimental animals by prolonged

administration of estrogen (Selye et al, 1935 : McEven et al., 1936; Zondedr, 1937: Fluhmann, 1955; Bo and Forks, 1957). Meissner and Sommers(1957) for the first time induced cystic and adenomatous hyperplasia, and adenocarcinoma in alloxan induced

diabetic rabbits. Many clinical observations suggested that prolonged and unopposed estrogen might produce sdenomatous hyperplasia, carcinoma in situ and carcinoma of endometrium (Gushers, 1947 :Fremont-Smith et al., 1946; Speert, 1948: Novak, 1951; Jenaen and Ostergward, 1954).

Many experimental studios and clinical observations indicate that endocrine factors play an important role in initiation and subsequent growth of neoplasm but there has been no evidence that estrogen can produce genuine fundal adenocarcinoma.

Many investigators have induced carcinoma of cervix and vagina in experimental animals by chemical carcinogens (Murphy,1953; Von Haam and Scarpell, 1956; lijima et al., 1964; Graham, 1969), but only a few reports about the endometrial tumor in experimental animals have been published Merriam et al., 1960: Shintani et al., 1966).

Recently investigators studied the effects of estrogen on the growth of tumor induced by 20-mcethylcholanthrene in the uterine cervix (Pannella and Gasbarrini. 1963 ; Alvizouri and Ramirez de Pita, 1964 ; Blanzat-Rebound and Russfield, 1969; Yada, 1969) but only few reports have appeared in the literature, which concerns

with the effects of estrogen on endemetrial lesions induced by 3-

methylcholanthrene,

The present investigation is aimed at studying 3-methylcholanthrene induced uterine endometrial changes in rat and discovering the possible correlation between bilateral oophorectomy and administration of estrogen on the 3-methylcholanthrene induced uterine endometrial changes in the same animal,

Materials and ethods

Female albino rata weighing around 200gm. wore used for the experiment. They are divided into four groups: (1) Control group which was subdivided into normal control, beeswax treated control and estrogen treated control group, (2) 3-methylcholanthrone treated group, (3) 3-methylcholanthrene combined with bilateral oophorectomy treated group and (4) 3-mcthylcholanthrene Combined With estrogen treated group.

For the 3-methylcholanthrene treated groups, the sterile cotten threads, soaked in melted beeswax containing one-third by weight of 3-mcthylcholanthrene, were inserted into both uterine horns and for the beeswax treated control group, the cotton threads soaked in malted beeswax into both uterine horns. For the estrogen treated groups, estradiol benzoate wag injected intramuscularly to the thigh one every week in a dost of 0.25 cc (5,000 IU) per kg. Bilateral oophorectomy were done by ligation of upper horn of uterus with silk, then removed the ovary together with its surrounding fat, the oviduct, and a small portion of the uterus. From each group 5 animals were killed at the 4th, 8th, 12th, and 24th week. Uterine thorns were removed at necropsy and examined for gross alteration, then the uterine horns were fixed in fixed in 10% neutral formalin, the tissue for higtologic and histochemical examination was fellowed by paraffin embedding. Sections for microscopic examination were cut in 6 μ thickness and awl sections were stained with hematoxylin and eosin method, periodic acid Schiff's reaction (PAS) for glycogen and glycoprotein, alcian blue strain for acid mucopolysaccharides, methyl-green pyronin method for RNA and Feulgen reaction for DNA.

Results and Summary

The endometrium in the normal control rat did not show any abnormal histologic findings except a mild degree of inflammatory cell infiltration. The animals receiving beeswax without 3-methylcholanthrene showed mild necrosis with chronic inflammatory reaction, and mild squamous metaplasia in surface epithelial cells and cystic dilatation of endometrial glands. The estrogen treated control animals showed moderate proliferation of surface columnar epithelium and cystic dilatation and mild hyperplasia of endometrial glands at the 24th week.

The animals receiving 3-methylcholanthrene showed mild necrosis wish inflammatory reaction and squamous metaplasia at the 4 th week, increased metaplasia with mild epithelial dyaplasia and mild endometrial hyperplasia at the 8th week, moderate endometrial hyperplasia with focal cystic glandular hyperplasia at the 12th week and the animals at the 24th week showed severe endomctrial hyperplasia with cystic and adenomatous hyperplasia, atypical adenomatous hyperplasia and malignant changes of the endometrial glands which were considered as adenocarcinoma.

The animals receiving 3-methylcholanthrene combined wish bilateral oophorcctomy showed similar histologic alteration as the animals receiving only 3-methylcholanthrene at the 4th and 8th week. Mild endometrial hyperplasia wish mild focal cystic glandular hyperplasia at the 12th week and moderate endometrial

hyperplasia with focal atypical hyperplasia without severe adenomatous or malignant changes at the 24th week.

The animals receiving 3-methylcholanthrene combined with estrogen showed mort incyeascdepithelial dysplasia at 7he 8 th wcck. Moderate cystic and adenomatous hyperplasia and typical polypoid growth of endometrium at the 12th week. Severe cystic and adenomatous hyperplasia, atypical adenomatous hyperplasia, and malignant changes and polypoid or papillary growth of endometrium at the 24th week.

The histochemical studies showed rare glycogen and glycoprotein in the crtoplasm of normal endometrial glandular epithelium but increased amounts in the areas of cystic and adenomatous hyperplasia and in malignant glandu1ar epithelial cells. The

acid mucopolysaccharides were seen