Reference SummaryMcAnulty PA, Toxicol Pathol 2005;33(5):609-20

Title

 Diethylstilbestrol (DES): carcinogenic potential in Xpa-/-, Xpa-/- / p53+/-, and wild-type mice during 9 months' dietary exposure.

Authors

 McAnulty PA; Skydsgaard M

Journal

 Toxicol Pathol

Volume

 33

Issue

 5

Year

 2005

Pages

 609-20

Abstract

 DES carcinogenicity has been investigated in 2 mouse knockout models, the Xpa homozygous knockout, and the combined Xpa homozygous and p53 heterozygous knockout. Wild-type (WT) mice were also included. Xpa mice received diets containing DES at concentrations of 0, 100, 300, and 1500 ppb for 39 weeks; Xpa/p53 and WT mice received diets containing 0 or 1500 ppb. There were 15 of each sex per group. Both Xpa and WT mice had a similar incidence of tumors at the high dosage of 1500 ppb, including pituitary adenomas in 4 WT mice and 7 Xpa mice, and single incidences of osteosarcoma (Xpa), T-cell lymphoma (WT and Xpa), and testicular interstitial cell adenoma (WT and Xpa). The incidence of tumors was higher in the Xpa/p53 mice at 1500 ppb, mainly attributable to 5 osteosarcomas in males and 2 in females, but also 4 pituitary adenomas, testicular interstitial cell adenomas in 4 males, and single incidences of cerebral glioma, phaeochromocytoma, and cervical fibrosarcoma. The incidence of osteosarcomas was related to the severity of fibro-osseous lesions in the bone marrow. It was concluded that for carcinogenicity screening, Xpa mice were no more sensitive than wild-type mice for compounds like DES, but the Xpa/p53 model showed an increased sensitivity.

Links

 J:101774 – MGI References
16178126 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs These mice had been backcrossed onto C57BL/6. The Trp53 allele was generated in a 129S2/SvPas background and the Xpa allele was generated in a 129P2/OlaHsd background.
These "mice were obtained from RIVM, Bilthoven, The Netherlands".
B6.129P2-Xpatm1Hvs These mice had been backcrossed onto C57BL/6. The Xpa allele was generated in a 129P2/OlaHsd background.
These "mice were obtained from RIVM, Bilthoven, The Netherlands".
C57BL/6JIco "C57BL/6 wild-type mice were obtained from IFFA Credo, l?Arbresle, France."

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
B6.129P2-Xpatm1Hvs Adrenal gland - Medulla pheochromocytoma Adrenal gland - Medulla

0
B6.129P2-Xpatm1Hvs Adrenal gland - Medulla pheochromocytoma
  • diethylstilbestrol (DES)
 Adrenal gland - Medulla

0
C57BL/6JIco Adrenal gland - Medulla pheochromocytoma Adrenal gland - Medulla

0
C57BL/6JIco Adrenal gland - Medulla pheochromocytoma
  • diethylstilbestrol (DES)
 Adrenal gland - Medulla

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Adrenal gland - Medulla pheochromocytoma Adrenal gland - Medulla

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Adrenal gland - Medulla pheochromocytoma
  • diethylstilbestrol (DES)
 Adrenal gland - Medulla

0 - 6.7
B6.129P2-Xpatm1Hvs Adrenal gland - Subcapsular cell hyperplasia Adrenal gland - Subcapsular cell

6.7 - 100
B6.129P2-Xpatm1Hvs Adrenal gland - Subcapsular cell hyperplasia
  • diethylstilbestrol (DES)
 Adrenal gland - Subcapsular cell

60 - 100
C57BL/6JIco Adrenal gland - Subcapsular cell hyperplasia Adrenal gland - Subcapsular cell

0 - 100
C57BL/6JIco Adrenal gland - Subcapsular cell hyperplasia
  • diethylstilbestrol (DES)
 Adrenal gland - Subcapsular cell

87 - 100
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Adrenal gland - Subcapsular cell hyperplasia Adrenal gland - Subcapsular cell

33 - 100
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Adrenal gland - Subcapsular cell hyperplasia
  • diethylstilbestrol (DES)
 Adrenal gland - Subcapsular cell

93
B6.129P2-Xpatm1Hvs Bone lesion Bone - Sternum

0 - 6.7
B6.129P2-Xpatm1Hvs Bone lesion Bone - Femur

0
B6.129P2-Xpatm1Hvs Bone lesion
  • diethylstilbestrol (DES)
 Bone - Sternum

0 - 60
B6.129P2-Xpatm1Hvs Bone lesion
  • diethylstilbestrol (DES)
 Bone - Femur

0 - 100
C57BL/6JIco Bone lesion Bone - Sternum

0
C57BL/6JIco Bone lesion Bone - Femur

0 - 13
C57BL/6JIco Bone lesion
  • diethylstilbestrol (DES)
 Bone - Sternum

13 - 27
C57BL/6JIco Bone lesion
  • diethylstilbestrol (DES)
 Bone - Femur

87 - 100
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Bone lesion Bone - Sternum

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Bone lesion Bone - Femur

0 - 6.7
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Bone lesion
  • diethylstilbestrol (DES)
 Bone - Sternum

53 - 60
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Bone lesion
  • diethylstilbestrol (DES)
 Bone - Femur

80
B6.129P2-Xpatm1Hvs Bone osteosarcoma Bone

0
B6.129P2-Xpatm1Hvs Bone osteosarcoma
  • diethylstilbestrol (DES)
 Bone

0
B6.129P2-Xpatm1Hvs Bone osteosarcoma
  • diethylstilbestrol (DES)
 Bone - Sternum

6.7
C57BL/6JIco Bone osteosarcoma Bone

0
C57BL/6JIco Bone osteosarcoma
  • diethylstilbestrol (DES)
 Bone

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Bone osteosarcoma Bone

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Bone osteosarcoma
  • diethylstilbestrol (DES)
 Bone

13 - 33
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Bone osteosarcoma
  • diethylstilbestrol (DES)
 Leg

27
B6.129P2-Xpatm1Hvs CNS - Brain - Cerebrum glioma CNS - Brain - Cerebrum

0
B6.129P2-Xpatm1Hvs CNS - Brain - Cerebrum glioma
  • diethylstilbestrol (DES)
 CNS - Brain - Cerebrum

0
C57BL/6JIco CNS - Brain - Cerebrum glioma CNS - Brain - Cerebrum

0
C57BL/6JIco CNS - Brain - Cerebrum glioma
  • diethylstilbestrol (DES)
 CNS - Brain - Cerebrum

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs CNS - Brain - Cerebrum glioma CNS - Brain - Cerebrum

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs CNS - Brain - Cerebrum glioma
  • diethylstilbestrol (DES)
 CNS - Brain - Cerebrum

0 - 6.7
B6.129P2-Xpatm1Hvs Connective tissue - Fibroblast fibrosarcoma Uterus - Cervix

0
B6.129P2-Xpatm1Hvs Connective tissue - Fibroblast fibrosarcoma
  • diethylstilbestrol (DES)
 Uterus - Cervix

0
C57BL/6JIco Connective tissue - Fibroblast fibrosarcoma Uterus - Cervix

0
C57BL/6JIco Connective tissue - Fibroblast fibrosarcoma
  • diethylstilbestrol (DES)
 Uterus - Cervix

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Connective tissue - Fibroblast fibrosarcoma Uterus - Cervix

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Connective tissue - Fibroblast fibrosarcoma
  • diethylstilbestrol (DES)
 Uterus - Cervix

6.7
B6.129P2-Xpatm1Hvs Forestomach papilloma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Forestomach

13
B6.129P2-Xpatm1Hvs Forestomach squamous cell carcinoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Forestomach

6.7
B6.129P2-Xpatm1Hvs Intestine - Large Intestine - Cecum adenoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Intestine - Large Intestine - Cecum

6.7
B6.129P2-Xpatm1Hvs Intestine - Small Intestine - Duodenum adenocarcinoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Intestine - Small Intestine - Duodenum

6.7
B6.129P2-Xpatm1Hvs Intestine - Small Intestine - Duodenum adenoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Intestine - Small Intestine - Duodenum

6.7
B6.129P2-Xpatm1Hvs Intestine - Small Intestine - Ileum adenocarcinoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Intestine - Small Intestine - Ileum

6.7
B6.129P2-Xpatm1Hvs Intestine - Small Intestine - Ileum adenoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Intestine - Small Intestine - Ileum

6.7
B6.129P2-Xpatm1Hvs Intestine - Small Intestine - Jejunum adenocarcinoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Intestine - Small Intestine - Jejunum

20
B6.129P2-Xpatm1Hvs Intestine - Small Intestine - Jejunum adenoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Intestine - Small Intestine - Jejunum

20
B6.129P2-Xpatm1Hvs Leukocyte - Lymphocyte - B-lymphocyte lymphoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Leukocyte - Lymphocyte - B-lymphocyte

13 - 20
B6.129P2-Xpatm1Hvs Leukocyte - Lymphocyte - T-lymphocyte lymphoma Leukocyte - Lymphocyte - T-lymphocyte

0
B6.129P2-Xpatm1Hvs Leukocyte - Lymphocyte - T-lymphocyte lymphoma
  • diethylstilbestrol (DES)
 Leukocyte - Lymphocyte - T-lymphocyte

0 - 6.7
B6.129P2-Xpatm1Hvs Leukocyte - Lymphocyte - T-lymphocyte lymphoma
  • benzo[a]pyrene (BP) (BaP) (B[a]P)
 Leukocyte - Lymphocyte - T-lymphocyte

6.7
C57BL/6JIco Leukocyte - Lymphocyte - T-lymphocyte lymphoma Leukocyte - Lymphocyte - T-lymphocyte

0
C57BL/6JIco Leukocyte - Lymphocyte - T-lymphocyte lymphoma
  • diethylstilbestrol (DES)
 Leukocyte - Lymphocyte - T-lymphocyte

0 - 6.7
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Leukocyte - Lymphocyte - T-lymphocyte lymphoma Leukocyte - Lymphocyte - T-lymphocyte

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Leukocyte - Lymphocyte - T-lymphocyte lymphoma
  • diethylstilbestrol (DES)
 Leukocyte - Lymphocyte - T-lymphocyte

0 - 13
B6.129P2-Xpatm1Hvs Mammary gland adenocarcinoma Mammary gland

0
B6.129P2-Xpatm1Hvs Mammary gland adenocarcinoma
  • diethylstilbestrol (DES)
 Mammary gland

0
C57BL/6JIco Mammary gland adenocarcinoma Mammary gland

0
C57BL/6JIco Mammary gland adenocarcinoma
  • diethylstilbestrol (DES)
 Mammary gland

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Mammary gland adenocarcinoma Mammary gland

6.7
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Mammary gland adenocarcinoma
  • diethylstilbestrol (DES)
 Mammary gland

0
B6.129P2-Xpatm1Hvs Mammary gland hyperplasia - focal Mammary gland

0
B6.129P2-Xpatm1Hvs Mammary gland hyperplasia - focal
  • diethylstilbestrol (DES)
 Mammary gland

0 - 73
C57BL/6JIco Mammary gland hyperplasia - focal Mammary gland

0
C57BL/6JIco Mammary gland hyperplasia - focal
  • diethylstilbestrol (DES)
 Mammary gland

67
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Mammary gland hyperplasia - focal Mammary gland

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Mammary gland hyperplasia - focal
  • diethylstilbestrol (DES)
 Mammary gland

67
B6.129P2-Xpatm1Hvs Pituitary gland - Pars distalis hyperplasia Pituitary gland - Pars distalis

0
B6.129P2-Xpatm1Hvs Pituitary gland - Pars distalis hyperplasia
  • diethylstilbestrol (DES)
 Pituitary gland - Pars distalis

0 - 87
C57BL/6JIco Pituitary gland - Pars distalis hyperplasia Pituitary gland - Pars distalis

0
C57BL/6JIco Pituitary gland - Pars distalis hyperplasia
  • diethylstilbestrol (DES)
 Pituitary gland - Pars distalis

80 - 87
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Pituitary gland - Pars distalis hyperplasia Pituitary gland - Pars distalis

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Pituitary gland - Pars distalis hyperplasia
  • diethylstilbestrol (DES)
 Pituitary gland - Pars distalis

73
B6.129P2-Xpatm1Hvs Pituitary gland - Pars intermedia hyperplasia Pituitary gland - Pars intermedia

0
B6.129P2-Xpatm1Hvs Pituitary gland - Pars intermedia hyperplasia
  • diethylstilbestrol (DES)
 Pituitary gland - Pars intermedia

0 - 53
C57BL/6JIco Pituitary gland - Pars intermedia hyperplasia Pituitary gland - Pars intermedia

0
C57BL/6JIco Pituitary gland - Pars intermedia hyperplasia
  • diethylstilbestrol (DES)
 Pituitary gland - Pars intermedia

47 - 67
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Pituitary gland - Pars intermedia hyperplasia Pituitary gland - Pars intermedia

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Pituitary gland - Pars intermedia hyperplasia
  • diethylstilbestrol (DES)
 Pituitary gland - Pars intermedia

33 - 47
B6.129P2-Xpatm1Hvs Pituitary gland adenoma Pituitary gland

0
B6.129P2-Xpatm1Hvs Pituitary gland adenoma
  • diethylstilbestrol (DES)
 Pituitary gland

0 - 33
C57BL/6JIco Pituitary gland adenoma Pituitary gland

0
C57BL/6JIco Pituitary gland adenoma
  • diethylstilbestrol (DES)
 Pituitary gland

13
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Pituitary gland adenoma Pituitary gland

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Pituitary gland adenoma
  • diethylstilbestrol (DES)
 Pituitary gland

13
B6.129P2-Xpatm1Hvs Prostate gland - Anterior lobe metaplasia - squamous Prostate gland - Anterior lobe

0
B6.129P2-Xpatm1Hvs Prostate gland - Anterior lobe metaplasia - squamous
  • diethylstilbestrol (DES)
 Prostate gland - Anterior lobe

0 - 60
C57BL/6JIco Prostate gland - Anterior lobe metaplasia - squamous Prostate gland - Anterior lobe

0
C57BL/6JIco Prostate gland - Anterior lobe metaplasia - squamous
  • diethylstilbestrol (DES)
 Prostate gland - Anterior lobe

87
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Prostate gland - Anterior lobe metaplasia - squamous Prostate gland - Anterior lobe

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Prostate gland - Anterior lobe metaplasia - squamous
  • diethylstilbestrol (DES)
 Prostate gland - Anterior lobe

40
B6.129P2-Xpatm1Hvs Testis - Leydig cell (Interstitial cell) adenoma Testis - Leydig cell (Interstitial cell)

0
B6.129P2-Xpatm1Hvs Testis - Leydig cell (Interstitial cell) adenoma
  • diethylstilbestrol (DES)
 Testis - Leydig cell (Interstitial cell)

0 - 20
C57BL/6JIco Testis - Leydig cell (Interstitial cell) adenoma Testis - Leydig cell (Interstitial cell)

0
C57BL/6JIco Testis - Leydig cell (Interstitial cell) adenoma
  • diethylstilbestrol (DES)
 Testis - Leydig cell (Interstitial cell)

6.7
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Testis - Leydig cell (Interstitial cell) adenoma Testis - Leydig cell (Interstitial cell)

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Testis - Leydig cell (Interstitial cell) adenoma
  • diethylstilbestrol (DES)
 Testis - Leydig cell (Interstitial cell)

27
B6.129P2-Xpatm1Hvs Testis - Leydig cell (Interstitial cell) hyperplasia Testis - Leydig cell (Interstitial cell)

0
B6.129P2-Xpatm1Hvs Testis - Leydig cell (Interstitial cell) hyperplasia
  • diethylstilbestrol (DES)
 Testis - Leydig cell (Interstitial cell)

0 - 67
C57BL/6JIco Testis - Leydig cell (Interstitial cell) hyperplasia Testis - Leydig cell (Interstitial cell)

0
C57BL/6JIco Testis - Leydig cell (Interstitial cell) hyperplasia
  • diethylstilbestrol (DES)
 Testis - Leydig cell (Interstitial cell)

53
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Testis - Leydig cell (Interstitial cell) hyperplasia Testis - Leydig cell (Interstitial cell)

0
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Testis - Leydig cell (Interstitial cell) hyperplasia
  • diethylstilbestrol (DES)
 Testis - Leydig cell (Interstitial cell)

60
B6.129P2-Xpatm1Hvs Uterus - Uterine gland hyperplasia
  • diethylstilbestrol (DES)
 Uterus - Uterine gland

observed
C57BL/6JIco Uterus - Uterine gland hyperplasia
  • diethylstilbestrol (DES)
 Uterus - Uterine gland

observed
B6.129-Trp53tm1Tyj/+ Xpatm1Hvs Uterus - Uterine gland hyperplasia
  • diethylstilbestrol (DES)
 Uterus - Uterine gland

observed