Rapid and high yield induction of endometrial adenocarcinomas in CD-1 mice by a single intrauterine administration of N-ethyl-N-nitrosourea combined with chronic 17 beta-estradiol treatment.
Induction of uterine endometrial adenocarcinomas in mice by N-ethyl-N-nitrosourea (ENU) and 17 beta-estradiol (E2) was examined. Illumination-induced persistent estrous CD-1 mice were divided into three groups at 10 weeks of age. Group 1 was given a single intra-uterine administration of polyethylene glycol (PEG) 1 week later, while Groups 2 and 3 received ENU (12.5 mg/kg), dissolved in PEG, in the same manner. Group 3 mice were also implanted with E2 pellets s.c. 1 week previously, and thereafter the pellets were renewed every 8 weeks throughout the experiment. At the termination (week 15 after the ENU treatment), all surviving mice were killed and the development of uterine proliferative lesions was assessed. All groups demonstrated endometrial hyperplasias, the severity being greatest in the ENU plus E2-treated animals (Group 3). The incidence of adenocarcinomas in Group 3 (20/29, 69%) was significantly higher than in Group 1 (0/25, 0%) or 2 (0/29, 0%). At 10 weeks after the ENU-treatment, serum E2 and progesterone concentrations in Group 3 were significantly higher and lower, respectively, than those in Groups 1 and 2. Consequently, the E2/progesterone (E2:P) ratio in Group 3 was significantly increased. These results indicate that a continuing high level of serum E2 and low level of progesterone are important for endometrial adenocarcinoma development in mice, with an increased E2:P ratio acting as a promoter for development of the endometrial lesions initiated by ENU treatment.
Takahashi
M
M
Department of Pathology, Sasaki Institute, Tokyo, Japan.
Iijima
T
T
Suzuki
K
K
Ando-Lu
J
J
Yoshida
M
M
Kitamura
T
T
Nishiyama
K
K
Miyajima
K
K
Maekawa
A
A
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D002273:Carcinogens; D003043:Cocarcinogenesis; D016889:Endometrial Neoplasms / Q000139:chemically induced* / Q000473:pathology; D004958:Estradiol / Q000097:blood; D004971:Estrus / Q000502:physiology; D005038:Ethylnitrosourea; D005260:Female; D008027:Light; D051379:Mice; D008815:Mice, Inbred Strains; D011374:Progesterone / Q000097:blood
D002273:Carcinogens; D011374:Progesterone; D004958:Estradiol; D005038:Ethylnitrosourea