Reference SummaryWaalkes MP, Cancer Res 2006 Feb 1;66(3):1337-45

Title

 Urogenital carcinogenesis in female CD1 mice induced by in utero arsenic exposure is exacerbated by postnatal diethylstilbestrol treatment.

Authors

 Waalkes MP; Liu J; Ward JM; Powell DA; Diwan BA

Journal

 Cancer Res

Volume

 66

Issue

 3

Year

 2006

Pages

 1337-45

Abstract

 Transplacental inorganic arsenic carcinogenicity, together with postnatal exposure to diethylstilbestrol or tamoxifen, was studied. Pregnant CD1 mice received 85 ppm arsenic in the drinking water from gestation days 8 to 18 and were allowed to give birth. Groups (n = 35) of female offspring were injected s.c. on postpartum days 1 through 5 with diethylstilbestrol (2 microg/pup/d) or tamoxifen (10 microg/pup/d) and observed for 90 weeks. Arsenic alone induced some urogenital system tumors, including mostly benign tumors of the ovary and uterus, and adrenal adenoma. Diethylstilbestrol alone induced some tumors (primarily cervical) but when given after in utero arsenic, it greatly enhanced urogenital tumor incidence, multiplicity, and progression. For instance, compared with the incidence of urogenital malignancies in the control (0%), arsenic alone (9%), and diethylstilbestrol alone (21%) groups, arsenic plus diethylstilbestrol acted synergistically, inducing a 48% incidence of malignant urogenital tumors. Of the urogenital tumors induced by arsenic plus diethylstilbestrol, 80% were malignant, and 55% were multiple site. Arsenic plus diethylstilbestrol increased ovarian, uterine, and vaginal tumors, and urinary bladder proliferative lesions, including three transitional cell carcinomas. Tamoxifen alone did not increase urogenital tumors or affect arsenic-induced neoplasia but did increase arsenic-induced uroepithelial proliferative lesions. Uterine and bladder carcinoma induced by arsenic plus diethylstilbestrol greatly overexpressed estrogen receptor-alpha (ER-alpha) and pS2, an estrogen-regulated gene. In neonatal uteri, prenatal arsenic increased ER-alpha expression and enhanced estrogen-related gene expression induced by postnatal diethylstilbestrol. Thus, arsenic acts with estrogens to enhance production of female mouse urogenital cancers.

Links

 J:106681 – MGI References
16452187 – National Library of Medicine/PubMed

Strain Notes

Strain Note
CD-1 These mice were purchased from Charles River.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
CD-1 Adrenal gland - Cortex adenoma Adrenal gland - Cortex

3.0
CD-1 Adrenal gland - Cortex adenoma
  • sodium arsenite
 Adrenal gland - Cortex

26
CD-1 Adrenal gland - Cortex adenoma
  • diethylstilbestrol (DES)
 Adrenal gland - Cortex

9.1
CD-1 Adrenal gland - Cortex adenoma
  • tamoxifen (TAM)
 Adrenal gland - Cortex

5.7
CD-1 Adrenal gland - Cortex adenoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Adrenal gland - Cortex

24
CD-1 Adrenal gland - Cortex adenoma
  • sodium arsenite
  • tamoxifen (TAM)
 Adrenal gland - Cortex

20
CD-1 Blood vessel hemangioma Ovary

0
CD-1 Blood vessel hemangioma Liver

0
CD-1 Blood vessel hemangioma
  • sodium arsenite
 Ovary

8.8
CD-1 Blood vessel hemangioma
  • sodium arsenite
 Liver

0
CD-1 Blood vessel hemangioma
  • diethylstilbestrol (DES)
 Ovary

0
CD-1 Blood vessel hemangioma
  • diethylstilbestrol (DES)
 Liver

0
CD-1 Blood vessel hemangioma
  • tamoxifen (TAM)
 Ovary

0
CD-1 Blood vessel hemangioma
  • tamoxifen (TAM)
 Liver

0
CD-1 Blood vessel hemangioma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Ovary

6.1
CD-1 Blood vessel hemangioma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Liver

3.0
CD-1 Blood vessel hemangioma
  • sodium arsenite
  • tamoxifen (TAM)
 Ovary

5.7
CD-1 Blood vessel hemangioma
  • sodium arsenite
  • tamoxifen (TAM)
 Liver

0
CD-1 Blood vessel hemangiosarcoma Uterus

0
CD-1 Blood vessel hemangiosarcoma Liver

0
CD-1 Blood vessel hemangiosarcoma
  • sodium arsenite
 Uterus

2.9
CD-1 Blood vessel hemangiosarcoma
  • sodium arsenite
 Liver

5.9
CD-1 Blood vessel hemangiosarcoma
  • diethylstilbestrol (DES)
 Uterus

0
CD-1 Blood vessel hemangiosarcoma
  • diethylstilbestrol (DES)
 Liver

0
CD-1 Blood vessel hemangiosarcoma
  • tamoxifen (TAM)
 Uterus

0
CD-1 Blood vessel hemangiosarcoma
  • tamoxifen (TAM)
 Liver

0
CD-1 Blood vessel hemangiosarcoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Uterus

0
CD-1 Blood vessel hemangiosarcoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Liver

0
CD-1 Blood vessel hemangiosarcoma
  • sodium arsenite
  • tamoxifen (TAM)
 Uterus

0
CD-1 Blood vessel hemangiosarcoma
  • sodium arsenite
  • tamoxifen (TAM)
 Liver

2.9
CD-1 Bone osteosarcoma
  • sodium arsenite
  • tamoxifen (TAM)
 Skin

2.9
CD-1 Intestine - Small Intestine adenoma
  • sodium arsenite
  • tamoxifen (TAM)
 Intestine - Small Intestine

2.9
CD-1 Kidney - Renal tubule hyperplasia - cystic
  • sodium arsenite
 Kidney - Renal tubule

2.9
CD-1 Kidney - Renal tubule hyperplasia - cystic
  • sodium arsenite
  • tamoxifen (TAM)
 Kidney - Renal tubule

2.9
CD-1 Kidney carcinoma Kidney

0
CD-1 Kidney carcinoma
  • sodium arsenite
 Kidney

0
CD-1 Kidney carcinoma
  • diethylstilbestrol (DES)
 Kidney

0
CD-1 Kidney carcinoma
  • tamoxifen (TAM)
 Kidney

0
CD-1 Kidney carcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Kidney

0
CD-1 Kidney carcinoma
  • sodium arsenite
  • tamoxifen (TAM)
 Kidney

2.9
CD-1 Kidney hyperplasia Kidney

0
CD-1 Kidney hyperplasia
  • diethylstilbestrol (DES)
 Kidney

0
CD-1 Kidney hyperplasia
  • tamoxifen (TAM)
 Kidney

0
CD-1 Kidney hyperplasia
  • sodium arsenite
  • diethylstilbestrol (DES)
 Kidney

0
CD-1 Leukocyte leukemia Leukocyte

3.0
CD-1 Leukocyte leukemia
  • sodium arsenite
  • diethylstilbestrol (DES)
 Leukocyte

3.0
CD-1 Leukocyte leukemia
  • sodium arsenite
  • tamoxifen (TAM)
 Leukocyte

2.9
CD-1 Leukocyte lymphoma Leukocyte

30
CD-1 Leukocyte lymphoma
  • sodium arsenite
 Leukocyte

5.9
CD-1 Leukocyte lymphoma
  • diethylstilbestrol (DES)
 Leukocyte

9.1
CD-1 Leukocyte lymphoma
  • tamoxifen (TAM)
 Leukocyte

17
CD-1 Leukocyte lymphoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Leukocyte

12
CD-1 Leukocyte lymphoma
  • sodium arsenite
  • tamoxifen (TAM)
 Leukocyte

29
CD-1 Liver - Bile duct cholangiocarcinoma Liver - Bile duct

0
CD-1 Liver - Bile duct cholangiocarcinoma
  • sodium arsenite
 Liver - Bile duct

2.9
CD-1 Liver - Bile duct cholangiocarcinoma
  • diethylstilbestrol (DES)
 Liver - Bile duct

0
CD-1 Liver - Bile duct cholangiocarcinoma
  • tamoxifen (TAM)
 Liver - Bile duct

0
CD-1 Liver - Bile duct cholangiocarcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Liver - Bile duct

0
CD-1 Liver - Bile duct cholangiocarcinoma
  • sodium arsenite
  • tamoxifen (TAM)
 Liver - Bile duct

0
CD-1 Liver hepatocellular adenoma Liver

0
CD-1 Liver hepatocellular adenoma
  • sodium arsenite
 Liver

2.9
CD-1 Liver hepatocellular adenoma
  • diethylstilbestrol (DES)
 Liver

3.0
CD-1 Liver hepatocellular adenoma
  • tamoxifen (TAM)
 Liver

0
CD-1 Liver hepatocellular adenoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Liver

9.1
CD-1 Liver hepatocellular adenoma
  • sodium arsenite
  • tamoxifen (TAM)
 Liver

8.6
CD-1 Liver hepatocellular carcinoma Liver

0
CD-1 Liver hepatocellular carcinoma
  • sodium arsenite
 Liver

0
CD-1 Liver hepatocellular carcinoma
  • diethylstilbestrol (DES)
 Liver

0
CD-1 Liver hepatocellular carcinoma
  • tamoxifen (TAM)
 Liver

0
CD-1 Liver hepatocellular carcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Liver

6.1
CD-1 Liver hepatocellular carcinoma
  • sodium arsenite
  • tamoxifen (TAM)
 Liver

0
CD-1 Lung adenocarcinoma Lung

12
CD-1 Lung adenocarcinoma
  • sodium arsenite
 Lung

15
CD-1 Lung adenocarcinoma
  • diethylstilbestrol (DES)
 Lung

6.1
CD-1 Lung adenocarcinoma
  • tamoxifen (TAM)
 Lung

11
CD-1 Lung adenocarcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Lung

21
CD-1 Lung adenocarcinoma
  • sodium arsenite
  • tamoxifen (TAM)
 Lung

14
CD-1 Lung adenoma Lung

15
CD-1 Lung adenoma
  • sodium arsenite
 Lung

21
CD-1 Lung adenoma
  • diethylstilbestrol (DES)
 Lung

9.1
CD-1 Lung adenoma
  • tamoxifen (TAM)
 Lung

5.7
CD-1 Lung adenoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Lung

6.1
CD-1 Lung adenoma
  • sodium arsenite
  • tamoxifen (TAM)
 Lung

8.6
CD-1 Mammary gland adenocarcinoma
  • sodium arsenite
 Mammary gland

2.9
CD-1 Mammary gland carcinoma Mammary gland

3.0
CD-1 Mesodermal cell/mesoblast myxosarcoma
  • diethylstilbestrol (DES)
 Mesodermal cell/mesoblast

3.0
CD-1 Mesodermal cell/mesoblast sarcoma Skin

3.0
CD-1 Mesodermal cell/mesoblast sarcoma
  • diethylstilbestrol (DES)
 Skin

3.0
CD-1 Muscle - Smooth leiomyosarcoma Uterus

0
CD-1 Muscle - Smooth leiomyosarcoma Uterus - Cervix

0
CD-1 Muscle - Smooth leiomyosarcoma
  • sodium arsenite
 Uterus

2.9
CD-1 Muscle - Smooth leiomyosarcoma
  • sodium arsenite
 Uterus - Cervix

0
CD-1 Muscle - Smooth leiomyosarcoma
  • diethylstilbestrol (DES)
 Uterus

0
CD-1 Muscle - Smooth leiomyosarcoma
  • diethylstilbestrol (DES)
 Uterus - Cervix

0
CD-1 Muscle - Smooth leiomyosarcoma
  • tamoxifen (TAM)
 Uterus

0
CD-1 Muscle - Smooth leiomyosarcoma
  • tamoxifen (TAM)
 Uterus - Cervix

0
CD-1 Muscle - Smooth leiomyosarcoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Uterus

0
CD-1 Muscle - Smooth leiomyosarcoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Uterus - Cervix

3.0
CD-1 Muscle - Smooth leiomyosarcoma
  • sodium arsenite
  • tamoxifen (TAM)
 Uterus

0
CD-1 Muscle - Smooth leiomyosarcoma
  • sodium arsenite
  • tamoxifen (TAM)
 Uterus - Cervix

0
CD-1 Muscle - Striated - Skeletal rhabdomyosarcoma
  • tamoxifen (TAM)
 Skin

2.9
CD-1 Muscle - Striated - Skeletal rhabdomyosarcoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Skin

3.0
CD-1 Myoepithelial cell myoepithelioma - malignant
  • sodium arsenite
  • diethylstilbestrol (DES)
 Salivary gland

3.0
CD-1 Ovary adenoma Ovary

0
CD-1 Ovary adenoma
  • sodium arsenite
 Ovary

12
CD-1 Ovary adenoma
  • diethylstilbestrol (DES)
 Ovary

6.1
CD-1 Ovary adenoma
  • tamoxifen (TAM)
 Ovary

2.9
CD-1 Ovary adenoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Ovary

18
CD-1 Ovary adenoma
  • sodium arsenite
  • tamoxifen (TAM)
 Ovary

2.9
CD-1 Ovary carcinoma Ovary

0
CD-1 Ovary carcinoma
  • sodium arsenite
 Ovary

0
CD-1 Ovary carcinoma
  • diethylstilbestrol (DES)
 Ovary

0
CD-1 Ovary carcinoma
  • tamoxifen (TAM)
 Ovary

0
CD-1 Ovary carcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Ovary

3.0
CD-1 Ovary carcinoma
  • sodium arsenite
  • tamoxifen (TAM)
 Ovary

5.7
CD-1 Oviduct adenoma Oviduct

0
CD-1 Oviduct adenoma
  • sodium arsenite
 Oviduct

0
CD-1 Oviduct adenoma
  • diethylstilbestrol (DES)
 Oviduct

3.0
CD-1 Oviduct adenoma
  • tamoxifen (TAM)
 Oviduct

2.9
CD-1 Oviduct adenoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Oviduct

6.1
CD-1 Oviduct adenoma
  • sodium arsenite
  • tamoxifen (TAM)
 Oviduct

8.6
CD-1 Oviduct carcinoma Oviduct

0
CD-1 Oviduct carcinoma
  • sodium arsenite
 Oviduct

0
CD-1 Oviduct carcinoma
  • diethylstilbestrol (DES)
 Oviduct

0
CD-1 Oviduct carcinoma
  • tamoxifen (TAM)
 Oviduct

0
CD-1 Oviduct carcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Oviduct

0
CD-1 Oviduct carcinoma
  • sodium arsenite
  • tamoxifen (TAM)
 Oviduct

0
CD-1 Oviduct hyperplasia Oviduct

15
CD-1 Oviduct hyperplasia
  • sodium arsenite
 Oviduct

79
CD-1 Oviduct hyperplasia
  • diethylstilbestrol (DES)
 Oviduct

73
CD-1 Oviduct hyperplasia
  • tamoxifen (TAM)
 Oviduct

86
CD-1 Oviduct hyperplasia
  • sodium arsenite
  • diethylstilbestrol (DES)
 Oviduct

79
CD-1 Oviduct hyperplasia
  • sodium arsenite
  • tamoxifen (TAM)
 Oviduct

71
CD-1 Thyroid gland adenocarcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Thyroid gland

3.0
CD-1 Urinary bladder - Transitional cell carcinoma - undifferentiated
  • sodium arsenite
  • diethylstilbestrol (DES)
 Urinary bladder - Transitional cell

observed
CD-1 Urinary bladder transitional cell carcinoma Urinary bladder

0
CD-1 Urinary bladder transitional cell carcinoma
  • sodium arsenite
 Urinary bladder

0
CD-1 Urinary bladder transitional cell carcinoma
  • diethylstilbestrol (DES)
 Urinary bladder

0
CD-1 Urinary bladder transitional cell carcinoma
  • tamoxifen (TAM)
 Urinary bladder

0
CD-1 Urinary bladder transitional cell carcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Urinary bladder

9.1
CD-1 Urinary bladder transitional cell carcinoma
  • sodium arsenite
  • tamoxifen (TAM)
 Urinary bladder

0
CD-1 Urinary bladder transitional cell hyperplasia Urinary bladder

3.0
CD-1 Urinary bladder transitional cell hyperplasia
  • sodium arsenite
 Urinary bladder

15
CD-1 Urinary bladder transitional cell hyperplasia
  • diethylstilbestrol (DES)
 Urinary bladder

3.0
CD-1 Urinary bladder transitional cell hyperplasia
  • tamoxifen (TAM)
 Urinary bladder

0
CD-1 Urinary bladder transitional cell hyperplasia
  • sodium arsenite
  • diethylstilbestrol (DES)
 Urinary bladder

30
CD-1 Urinary bladder transitional cell hyperplasia
  • sodium arsenite
  • tamoxifen (TAM)
 Urinary bladder

26
CD-1 Urinary bladder transitional cell papilloma Urinary bladder

0
CD-1 Urinary bladder transitional cell papilloma
  • sodium arsenite
 Urinary bladder

0
CD-1 Urinary bladder transitional cell papilloma
  • diethylstilbestrol (DES)
 Urinary bladder

0
CD-1 Urinary bladder transitional cell papilloma
  • tamoxifen (TAM)
 Urinary bladder

0
CD-1 Urinary bladder transitional cell papilloma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Urinary bladder

0
CD-1 Urinary bladder transitional cell papilloma
  • sodium arsenite
  • tamoxifen (TAM)
 Urinary bladder

2.9
CD-1 Uterus - Cervix adenoma Uterus - Cervix

0
CD-1 Uterus - Cervix adenoma
  • sodium arsenite
 Uterus - Cervix

0
CD-1 Uterus - Cervix adenoma
  • diethylstilbestrol (DES)
 Uterus - Cervix

0
CD-1 Uterus - Cervix adenoma
  • tamoxifen (TAM)
 Uterus - Cervix

0
CD-1 Uterus - Cervix adenoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Uterus - Cervix

0
CD-1 Uterus - Cervix adenoma
  • sodium arsenite
  • tamoxifen (TAM)
 Uterus - Cervix

0
CD-1 Uterus - Cervix carcinoma Uterus - Cervix

0
CD-1 Uterus - Cervix carcinoma
  • sodium arsenite
 Uterus - Cervix

0
CD-1 Uterus - Cervix carcinoma
  • diethylstilbestrol (DES)
 Uterus - Cervix

18
CD-1 Uterus - Cervix carcinoma
  • tamoxifen (TAM)
 Uterus - Cervix

0
CD-1 Uterus - Cervix carcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Uterus - Cervix

24
CD-1 Uterus - Cervix carcinoma
  • sodium arsenite
  • tamoxifen (TAM)
 Uterus - Cervix

0
CD-1 Uterus - Cervix squamous cell carcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Uterus - Cervix

observed
CD-1 Uterus adenocarcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Uterus

observed
CD-1 Uterus adenoma Uterus

0
CD-1 Uterus adenoma
  • sodium arsenite
 Uterus

8.8
CD-1 Uterus adenoma
  • diethylstilbestrol (DES)
 Uterus

0
CD-1 Uterus adenoma
  • tamoxifen (TAM)
 Uterus

0
CD-1 Uterus adenoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Uterus

0
CD-1 Uterus adenoma
  • sodium arsenite
  • tamoxifen (TAM)
 Uterus

0
CD-1 Uterus carcinoma Uterus

0
CD-1 Uterus carcinoma
  • sodium arsenite
 Uterus

5.9
CD-1 Uterus carcinoma
  • diethylstilbestrol (DES)
 Uterus

0
CD-1 Uterus carcinoma
  • tamoxifen (TAM)
 Uterus

5.7
CD-1 Uterus carcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Uterus

21
CD-1 Uterus carcinoma
  • sodium arsenite
  • tamoxifen (TAM)
 Uterus

5.7
CD-1 Vagina adenoma Vagina

0
CD-1 Vagina adenoma
  • sodium arsenite
 Vagina

0
CD-1 Vagina adenoma
  • diethylstilbestrol (DES)
 Vagina

0
CD-1 Vagina adenoma
  • tamoxifen (TAM)
 Vagina

0
CD-1 Vagina adenoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Vagina

0
CD-1 Vagina adenoma
  • sodium arsenite
  • tamoxifen (TAM)
 Vagina

0
CD-1 Vagina carcinoma Vagina

0
CD-1 Vagina carcinoma
  • sodium arsenite
 Vagina

0
CD-1 Vagina carcinoma
  • diethylstilbestrol (DES)
 Vagina

3.0
CD-1 Vagina carcinoma
  • tamoxifen (TAM)
 Vagina

0
CD-1 Vagina carcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Vagina

15
CD-1 Vagina carcinoma
  • sodium arsenite
  • tamoxifen (TAM)
 Vagina

0
CD-1 Vagina squamous cell carcinoma
  • sodium arsenite
  • diethylstilbestrol (DES)
 Vagina

observed