Preventive effects of danazol on endometrial carcinogenesis in mice.
Short and long-term experiments were designed to determine effects of danazol on estrogen-related endometrial carcinogenesis in mice. The short-term assays showed that danazol decreased expression levels of c-fos/jun mRNA and their oncoproteins induced by estradiol-17beta (E2). For the long-term assay, 85 female ICR mice were given N-methyl-N-nitrsourea solution into their uterine corpora. The animals were divided into three groups as follows: Group 1, E2-diet (5 ppm) plus danazol (2 mg/body (s.c.), every 4 weeks); Group 2, E2-diet alone, Group 3, basal diet alone. At 30 weeks, incidences of atypical and complex endometrial hyperplasia were significantly decreased by danazol-treatment. These results suggest that danazol has preventive effects on estrogen-related endometrial carcinogenesis in mice, through the suppression of estrogen-induced c-fos/jun-expression.
Niwa
K
K
Department of Obstetrics and Gynecology, Gifu University School of Medicine, 40 Tsukasa-machi, 500-8705, Gifu, Japan. kniwa@cc.gifu-u.ac.jp
Hashimoto
M
M
Morishita
S
S
Yokoyama
Y
Y
Lian
Z
Z
Tagami
K
K
Mori
H
H
Tamaya
T
T
D000284:Administration, Oral; D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D003613:Danazol / Q000627:therapeutic use*; D016889:Endometrial Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007150:Immunohistochemistry; D008770:Methylnitrosourea / Q000633:toxicity; D051379:Mice; D008813:Mice, Inbred ICR; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D014599:Uterus / Q000737:chemistry / Q000473:pathology
D000477:Alkylating Agents; D004965:Estrogen Antagonists; D018809:Proliferating Cell Nuclear Antigen; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D004958:Estradiol; D008770:Methylnitrosourea; D003613:Danazol