Reference SummaryNiwa K, Jpn J Cancer Res 1998 May;89(5):502-9

Title

 Effects of tamoxifen on endometrial carcinogenesis in mice.

Authors

 Niwa K; Morishita S; Hashimoto M; Itoh T; Fujimoto J; Mori H; Tamaya T

Journal

 Jpn J Cancer Res

Volume

 89

Issue

 5

Year

 1998

Pages

 502-9

Abstract

 Two experiments were conducted to determine the effect of tamoxifen (TAM) in mouse endometrium in comparison with that of 17beta-estradiol (E2). In a medium-term assay, TAM as well as E2 treatment semi-dose-dependently increased the levels of fos/jun mRNA and their oncoproteins (Fos/Jun). The long-term effect of TAM on mouse endometrial carcinogenesis was also examined in the following model. A total of 150 female ICR mice, 12-13 weeks of age, were used. Of these, 125 mice received an injection of N-methyl-N-nitosourea (MNU) solution (1 mg/100 g body weight) into their left uterine tube and saline into the right. One week later, they were divided into four groups: groups 1 (35 mice) and 2 (30 mice) were given 25 ppm and ppm E2-containing diet, respectively, while group 3 (30 mice) was fed 5 ppm TAM-containing diet. Group 5 (30 mice) was fed basal diet alone. The remaining 25 mice (group 4) received 5 ppm TAM-containing diet alone. At the termination of the experiment (30 weeks), endometrial carcinomas were confirmed to be present in the groups exposed to MNU. TAM increased the incidence of preneoplastic lesions of the endometrium, while E2 enhanced the occurrence of the carcinoma. No carcinomas were found in the group given TAM alone. In the ovaries, corpora lutea were lacking in most of the mice exposed to TAM, suggesting that the animals were not cycling. Such findings indicated that TAM has an enhancing effect on endometrial carcinogenesis in mice, probably via a mechanism involving overexpression of Fos/Jun proteins.

Links

 J:48614 – MGI References
9685853 – National Library of Medicine/PubMed

Strain Notes

Strain Note
ICR The mice in this study were from Japan SLC Co., Shizuoka, Japan.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
ICR Ovary cyst
  • 17beta-estradiol (E2)
  • N-methyl-N-nitrosourea (MNU)
 Ovary

33.0 - 53.0
ICR Ovary cyst
  • N-methyl-N-nitrosourea (MNU)
  • tamoxifen (TAM)
 Ovary

24.0 - 25.0
ICR Ovary cyst
  • tamoxifen (TAM)
 Ovary

62.0 - 69.0
ICR Ovary cyst
  • N-methyl-N-nitrosourea (MNU)
 Ovary

14.0 - 20.0
ICR Ovary tumor
  • 17beta-estradiol (E2)
  • N-methyl-N-nitrosourea (MNU)
 Ovary

0
ICR Ovary tumor
  • N-methyl-N-nitrosourea (MNU)
  • tamoxifen (TAM)
 Ovary

0
ICR Ovary tumor
  • tamoxifen (TAM)
 Ovary

0
ICR Ovary tumor
  • N-methyl-N-nitrosourea (MNU)
 Ovary

0
ICR Oviduct hyperplasia
  • 17beta-estradiol (E2)
  • N-methyl-N-nitrosourea (MNU)
 Oviduct

55.0 - 94.0
ICR Oviduct hyperplasia
  • N-methyl-N-nitrosourea (MNU)
  • tamoxifen (TAM)
 Oviduct

100
ICR Oviduct hyperplasia
  • tamoxifen (TAM)
 Oviduct

100
ICR Oviduct hyperplasia
  • N-methyl-N-nitrosourea (MNU)
 Oviduct

11
ICR Oviduct tumor
  • 17beta-estradiol (E2)
  • N-methyl-N-nitrosourea (MNU)
 Oviduct

0
ICR Oviduct tumor
  • N-methyl-N-nitrosourea (MNU)
  • tamoxifen (TAM)
 Oviduct

0
ICR Oviduct tumor
  • tamoxifen (TAM)
 Oviduct

0
ICR Oviduct tumor
  • N-methyl-N-nitrosourea (MNU)
 Oviduct

0
ICR Uterus - Endometrium adenocarcinoma
  • 17beta-estradiol (E2)
  • N-methyl-N-nitrosourea (MNU)
 Uterus - Endometrium

38 - 67
ICR Uterus - Endometrium adenocarcinoma
  • N-methyl-N-nitrosourea (MNU)
  • tamoxifen (TAM)
 Uterus - Endometrium

17
ICR Uterus - Endometrium adenocarcinoma
  • tamoxifen (TAM)
 Uterus - Endometrium

0
ICR Uterus - Endometrium adenocarcinoma
  • N-methyl-N-nitrosourea (MNU)
 Uterus - Endometrium

12
ICR Uterus - Endometrium hyperplasia - atypical
  • 17beta-estradiol (E2)
  • N-methyl-N-nitrosourea (MNU)
 Uterus - Endometrium

67 - 83
ICR Uterus - Endometrium hyperplasia - atypical
  • N-methyl-N-nitrosourea (MNU)
  • tamoxifen (TAM)
 Uterus - Endometrium

63
ICR Uterus - Endometrium hyperplasia - atypical
  • tamoxifen (TAM)
 Uterus - Endometrium

5
ICR Uterus - Endometrium hyperplasia - atypical
  • N-methyl-N-nitrosourea (MNU)
 Uterus - Endometrium

38
ICR Uterus - Endometrium hyperplasia - complex
  • 17beta-estradiol (E2)
  • N-methyl-N-nitrosourea (MNU)
 Uterus - Endometrium

96 - 97
ICR Uterus - Endometrium hyperplasia - complex
  • N-methyl-N-nitrosourea (MNU)
  • tamoxifen (for inducing expression from mutant alleles)
 Uterus - Endometrium

92
ICR Uterus - Endometrium hyperplasia - complex
  • tamoxifen (TAM)
 Uterus - Endometrium

57
ICR Uterus - Endometrium hyperplasia - complex
  • N-methyl-N-nitrosourea (MNU)
 Uterus - Endometrium

76
ICR Uterus - Endometrium hyperplasia - simple
  • 17beta-estradiol (E2)
  • N-methyl-N-nitrosourea (MNU)
 Uterus - Endometrium

92 - 97
ICR Uterus - Endometrium hyperplasia - simple
  • N-methyl-N-nitrosourea (MNU)
  • tamoxifen (TAM)
 Uterus - Endometrium

96
ICR Uterus - Endometrium hyperplasia - simple
  • tamoxifen (TAM)
 Uterus - Endometrium

96
ICR Uterus - Endometrium hyperplasia - simple
  • N-methyl-N-nitrosourea (MNU)
 Uterus - Endometrium

18
ICR Vagina tumor
  • 17beta-estradiol (E2)
  • N-methyl-N-nitrosourea (MNU)
 Vagina

0
ICR Vagina tumor
  • N-methyl-N-nitrosourea (MNU)
  • tamoxifen (TAM)
 Vagina

0
ICR Vagina tumor
  • tamoxifen (TAM)
 Vagina

0
ICR Vagina tumor
  • N-methyl-N-nitrosourea (MNU)
 Vagina

0