Time-dependent promotion activity of 17beta-estradiol on uterine carcinogenesis in mice initiated with N-ethyl-N-nitrosourea.
The time-dependent promotion activity of 17beta-estradiol (E2) by initiation with N-ethyl-N-nitrosourea (ENU) on induction of mouse uterine endometrial proliferative lesions was examined. Illumination-induced persistent estrous female CD-1 mice were divided into five groups at 9 weeks of age. At 10 weeks of age, mice in all groups (n=25) were given a single intra-uterine administration of ENU (50 mg/kg), dissolved in polyethylene glycol. Animals in Groups 2 to 5 were then implanted s.c. with an E2 pellet at 9, 11, 14 and 17 weeks of age. The implants were left in place for 8 weeks and then taken out. At the termination of the experiment (week 15 after the ENU-treatment), all surviving mice were killed and the development of uterine proliferative lesions were assessed. All groups demonstrated endometrial hyperplasias and adenocarcinomas and the incidences of the latter in ENU plus E2 treated animals (Groups 2 to 5; 36, 48, 35 and 36%, respectively) were significantly higher compared to 8% for Group 1, without any variation with the age at E2 treatment. However, the incidences of adenocarcinomas plus severe hyperplasias increased from Groups 1 to 5 (28, 40, 56; P<0.05, 61; P<0.05 and 80%; P<0.01, respectively), indicating that promotion effects of E2 on induction of uterine proliferative lesions in the uterine endometrium become more pronounced with the interval after ENU initiation.
Department of Pathology, Sasaki Institute, 2-2 Kanda-Surugadai, Chiyoda-ku, 101-0062, Tokyo, Japan.
M
M
Takahashi
S
S
Nishimura
K
K
Miyajima
K
K
Sasahara
M
M
Yoshida
J
J
Ando
A
A
Maekawa
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism; D000367:Age Factors; D000477:Alkylating Agents; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D018450:Disease Progression; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005038:Ethylnitrosourea; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D011374:Progesterone / Q000097:blood; D013997:Time Factors; D014594:Uterine Neoplasms / Q000139:chemically induced* / Q000378:metabolism*
D000477:Alkylating Agents; D002273:Carcinogens; D011374:Progesterone; D004958:Estradiol; D005038:Ethylnitrosourea