Biomaterial Database

Endometrial carcinogenesis induced by concurrent oral administration of ethylenethiourea and sodium nitrite in mice. 1994

A Yoshida, and T Harada, and S Hayashi, and I Mori, and H Miyajima, and K Maita

Toxicology Division, Mitsukaido Laboratories, Institute of Environmental Toxicology, Ibaraki, Japan.

Endometrial carcinogenesis induced by concurrent oral administration of ethylenethiourea (ETU) and sodium nitrite (NaNO2) was investigated in ICR (Crj:CD-1) female mice. A mixed solution of ETU (100 mg/kg) and NaNO2 (70 mg/kg) was given to animals orally once a week for up to 6 months and all surviving animals were killed at 12 months of study. During the study, estrous cycle was monitored by vaginal smear and five or 10 selected animals were subjected to interim killing at 3 month interval to observe time-related carcinogenic responses of the uterus. Treatment with ETU and NaNO2 resulted in development of endometrial adenocarcinomas in the uterine horn and the incidence reached 42% in the surviving animals at 12 months. Prior to the development of the tumor, atypical hyperplasia of endometrial glands was frequently observed and regarded as the precancerous lesion. Immunohistochemistry for bromodeoxyuridine (BrdU) incorporation revealed higher labeling indices in both hyperplastic and neoplastic endometrial glandular cells, and the index in the adenocarcinoma was more than 20% on average at any stage of the estrous cycle. Overexpression of p53 protein, which is frequently demonstrated in virulent phenotypes of human corpus cancers, was seen in three out of eight (38%) adenocarcinomas, but not in the atypical hyperplasia or normal endometrial glands. There were no treatment-related changes in the estrous cycle on vaginal smears at any interval of the study. The analyses for plasma ovarian hormones at 12 months disclosed a marked depression of progesterone in the treated animals, while the 17 beta-estradiol (E2) level was comparable to the controls. These results suggest that endometrial carcinogenesis by ETU and NaNO2 could be initiated with atypical hyperplasia of the endometrial gland and a decrease in plasma progesterone level may play an important role in the development of endometrial carcinogenesis. In addition, inactivation of the p53 gene may play a significant role in the malignant transformation of endometrial epithelial cells in mice.

UI	MeSH Term	Description	Entries
D007150	Immunohistochemistry	Histochemical localization of immunoreactive substances using labeled antibodies as reagents.	Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D009929	Organ Size	The measurement of an organ in volume, mass, or heaviness.	Organ Volume,Organ Weight,Size, Organ,Weight, Organ
D010053	Ovary	The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE.	Ovaries
D001973	Bromodeoxyuridine	A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.	BUdR,BrdU,Bromouracil Deoxyriboside,Broxuridine,5-Bromo-2'-deoxyuridine,5-Bromodeoxyuridine,NSC-38297,5 Bromo 2' deoxyuridine,5 Bromodeoxyuridine,Deoxyriboside, Bromouracil
D003043	Cocarcinogenesis	The combination of two or more different factors in the production of cancer.	Cocarcinogeneses
D004971	Estrus	The period in the ESTROUS CYCLE associated with maximum sexual receptivity and fertility in non-primate female mammals.
D005031	Ethylenethiourea	A degradation product of ethylenebis(dithiocarbamate) fungicides. It has been found to be carcinogenic and to cause THYROID hyperplasia.	Imidazolidinethione,2-Mercaptoimidazoline,Imidazolidine-2-thione,2 Mercaptoimidazoline
D005260	Female		Females
D000230	Adenocarcinoma	A malignant epithelial tumor with a glandular organization.	Adenocarcinoma, Basal Cell,Adenocarcinoma, Granular Cell,Adenocarcinoma, Oxyphilic,Adenocarcinoma, Tubular,Adenoma, Malignant,Carcinoma, Cribriform,Carcinoma, Granular Cell,Carcinoma, Tubular,Adenocarcinomas,Adenocarcinomas, Basal Cell,Adenocarcinomas, Granular Cell,Adenocarcinomas, Oxyphilic,Adenocarcinomas, Tubular,Adenomas, Malignant,Basal Cell Adenocarcinoma,Basal Cell Adenocarcinomas,Carcinomas, Cribriform,Carcinomas, Granular Cell,Carcinomas, Tubular,Cribriform Carcinoma,Cribriform Carcinomas,Granular Cell Adenocarcinoma,Granular Cell Adenocarcinomas,Granular Cell Carcinoma,Granular Cell Carcinomas,Malignant Adenoma,Malignant Adenomas,Oxyphilic Adenocarcinoma,Oxyphilic Adenocarcinomas,Tubular Adenocarcinoma,Tubular Adenocarcinomas,Tubular Carcinoma,Tubular Carcinomas
D000284	Administration, Oral	The giving of drugs, chemicals, or other substances by mouth.	Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations