Reference SummaryDiwan BA, Toxicol Appl Pharmacol 1999 Nov 15;161(1):82-99

Title

 Multiorgan transplacental and neonatal carcinogenicity of 3'-azido-3'-deoxythymidine in mice.

Authors

 Diwan BA; Riggs CW; Logsdon D; Haines DC; Olivero OA; Rice JM; Yuspa SH; Poirier MC; Anderson LM

Journal

 Toxicol Appl Pharmacol

Volume

 161

Issue

 1

Year

 1999

Pages

 82-99

Abstract

 The anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) is used successfully for reduction of perinatal viral transmission. However toxic side effects including carcinogenesis are possible. To test this, pregnant CD-1 Swiss mice were given 25.0 or 12.5 mg AZT on gestation days 12-18. Previously we reported an increase in lung, liver, and female reproductive system tumors in offspring euthanized at 1 year (Olivero et al., J. Natl. Cancer Inst. 89, 1602-1608, 1997). Findings for all remaining offspring up to 2 years old are reported here. AZT effects were most prominent in female offspring, with a significant threefold increase in lung tumors, a reduction in lymphoblastic and follicle center cell lymphomas, and a significant increase in histiocytic sarcomas (0 in controls, 3% after low-dose AZT, and 8% after high-dose AZT, p = 0.022). Dose-dependent incidences of mammary gland, ovarian, and seminal vesicle tumors were low but significant: 0/106 controls, 3/105 low-dose, and 8/105 high-dose mice presented one of these neoplasms (p = 0.0025). Incidences of females showing any clearly AZT-related neoplasm, in lung, liver, ovary, or mammary gland or histiocytic sarcoma, in the second year, were 12/32 after the low dose and 14/27 after the high dose vs 3/23 controls (p = 0.0045). Also, the sensitivity of neonatal mice was assessed by administration of 25, 50, 100, or 200 mg/kg AZT on postnatal days 1 through 8. The effects at 2 years were similar to those seen after transplacental exposure, with significant increases in lung, liver, and mammary tumors in females. The results confirm that AZT is a moderately effective perinatal carcinogen in mice, targeting several tissue types.

Links

 J:59552 – MGI References
10558926 – National Library of Medicine/PubMed

Strain Notes

Strain Note
CD-1 "Male and female CD-1 mice 6-8 weeks old were obtained from Charles River, Inc. (Raleigh, NC)."

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
CD-1 Adipose tissue lipoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Peritoneum - Mesentery

1.9
CD-1 Adrenal gland - Cortex adenoma Adrenal gland - Cortex

1.9
CD-1 Adrenal gland - Medulla pheochromocytoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Adrenal gland - Medulla

2.0
CD-1 Adrenal gland - Medulla pheochromocytoma
  • sodium barbital (BB)
 Adrenal gland - Medulla

2.9
CD-1 Adrenal gland tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Adrenal gland

0.9
CD-1 Blood vessel hemangiosarcoma Uterus

4.3
CD-1 Blood vessel hemangiosarcoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Uterus

4.2
CD-1 Blood vessel hemangiosarcoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Blood vessel

observed
CD-1 Blood vessel tumor Blood vessel

10.0 - 20.0
CD-1 Blood vessel tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Blood vessel

10.0 - 20.0
CD-1 Blood vessel tumor
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Blood vessel

10.0 - 20.0
CD-1 Blood vessel tumor
  • sodium barbital (BB)
 Blood vessel

10.0 - 20.0
CD-1 Bone osteosarcoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Stomach - Glandular

2.0
CD-1 Bone osteosarcoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Subcutis

1.9
CD-1 Connective tissue - Fibroblast fibrosarcoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Seminal vesicle

7.1
CD-1 Eye - Harderian gland adenoma Eye - Harderian gland

1.9
CD-1 Forestomach tumor Forestomach

0
CD-1 Forestomach tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Forestomach

observed - 3.7
CD-1 Intestine - Small Intestine adenocarcinoma Intestine - Small Intestine

1.9
CD-1 Intestine - Small Intestine adenoma Intestine - Small Intestine

1.9
CD-1 Kidney adenoma Kidney

1.9
CD-1 Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell lymphoma Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell

6.5 - 34.8
CD-1 Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell lymphoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell

0 - 21.4
CD-1 Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell lymphoma
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell

0 - 30.4
CD-1 Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell lymphoma
  • sodium barbital (BB)
 Leukocyte - Lymphocyte - B-lymphocyte - Follicular center cell

0 - 20
CD-1 Leukocyte - Lymphocyte - T-lymphocyte lymphoma - lymphoblastic Leukocyte - Lymphocyte - T-lymphocyte

3.2 - 12.9
CD-1 Leukocyte - Lymphocyte - T-lymphocyte lymphoma - lymphoblastic
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte - Lymphocyte - T-lymphocyte

0 - 25
CD-1 Leukocyte - Lymphocyte - T-lymphocyte lymphoma - lymphoblastic
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte - Lymphocyte - T-lymphocyte

7.7 - 14.3
CD-1 Leukocyte - Lymphocyte - T-lymphocyte lymphoma - lymphoblastic
  • sodium barbital (BB)
 Leukocyte - Lymphocyte - T-lymphocyte

0 - 25
CD-1 Leukocyte - Lymphocyte - Thymocyte lymphoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Thymus

0 - 7.1
CD-1 Leukocyte - Lymphocyte leukemia - lymphocytic Leukocyte - Lymphocyte

0
CD-1 Leukocyte - Lymphocyte leukemia - lymphocytic
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte - Lymphocyte

0 - 3.7
CD-1 Leukocyte - Lymphocyte leukemia - lymphocytic
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte - Lymphocyte

0
CD-1 Leukocyte - Lymphocyte leukemia - lymphocytic
  • sodium barbital (BB)
 Leukocyte - Lymphocyte

0
CD-1 Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Uterus

4.2
CD-1 Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma Leukocyte - Monocyte - Macrophage - Histiocyte

0 - 3.2
CD-1 Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte - Monocyte - Macrophage - Histiocyte

0 - 11.1
CD-1 Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte - Monocyte - Macrophage - Histiocyte

0 - 4.3
CD-1 Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma
  • sodium barbital (BB)
 Leukocyte - Monocyte - Macrophage - Histiocyte

0
CD-1 Leukocyte - Myelocyte (Granulocyte) leukemia - myelocytic Leukocyte - Myelocyte (Granulocyte)

0 - 4.3
CD-1 Leukocyte - Myelocyte (Granulocyte) leukemia - myelocytic
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte - Myelocyte (Granulocyte)

0 - 3.8
CD-1 Leukocyte - Myelocyte (Granulocyte) leukemia - myelocytic
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte - Myelocyte (Granulocyte)

0
CD-1 Leukocyte - Myelocyte (Granulocyte) leukemia - myelocytic
  • sodium barbital (BB)
 Leukocyte - Myelocyte (Granulocyte)

0
CD-1 Leukocyte lymphoma Leukocyte

0 - 9.5
CD-1 Leukocyte lymphoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte

0
CD-1 Leukocyte lymphoma
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte

0 - 4.3
CD-1 Leukocyte lymphoma
  • sodium barbital (BB)
 Leukocyte

0
CD-1 Leukocyte lymphoma - immunoblastic Leukocyte

0 - 9.5
CD-1 Leukocyte lymphoma - immunoblastic
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte

0 - 6.25
CD-1 Leukocyte lymphoma - immunoblastic
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Leukocyte

0
CD-1 Leukocyte lymphoma - immunoblastic
  • sodium barbital (BB)
 Leukocyte

0
CD-1 Liver adenoma Liver

0 - 25
CD-1 Liver adenoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Liver

0 - 66.7
CD-1 Liver carcinoma Liver

0 - 40
CD-1 Liver carcinoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Liver

0 - 37.5
CD-1 Liver hepatoblastoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Liver

14.8
CD-1 Liver tumor Liver

0 - 60
CD-1 Liver tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Liver

0 - 83.3
CD-1 Lung adenoma Lung

0 - 40
CD-1 Lung adenoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Lung

4.8 - 52.6
CD-1 Lung carcinoma Lung

0 - 20
CD-1 Lung carcinoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Lung

4.3 - 40
CD-1 Lung tumor Lung

0 - 60
CD-1 Lung tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Lung

13.0 - 87.5
CD-1 Mammary gland adenocarcinoma Mammary gland

0
CD-1 Mammary gland adenocarcinoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Mammary gland

0 - 25
CD-1 Mammary gland adenocarcinoma
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Mammary gland

0 - 13.0
CD-1 Mammary gland adenocarcinoma
  • sodium barbital (BB)
 Mammary gland

0 - 5.0
CD-1 Mammary gland tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Mammary gland

0 - 16.7
CD-1 Mesodermal cell/mesoblast sarcoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Skin

2.0
CD-1 Mesodermal cell/mesoblast sarcoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Intestine - Small Intestine

1.9
CD-1 Mesodermal cell/mesoblast sarcoma
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Abdominal cavity

2.7
CD-1 Muscle - Smooth leiomyoma Uterus - Cervix

4.3
CD-1 Muscle - Smooth leiomyosarcoma Uterus

4.3
CD-1 Muscle - Smooth leiomyosarcoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Vagina

4.5
CD-1 Muscle - Smooth leiomyosarcoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Uterus

3.7
CD-1 Muscle - Smooth leiomyosarcoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Intestine - Large Intestine - Colon

2.0
CD-1 Ovary - Granulosa cell tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Ovary - Granulosa cell

3.1
CD-1 Ovary - Sertoli cell tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Ovary - Sertoli cell

4.2
CD-1 Ovary - Theca cell thecoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Ovary - Theca cell

3.7
CD-1 Ovary - Theca cell tumor
  • sodium barbital (BB)
 Ovary - Theca cell

5.0
CD-1 Ovary cystadenoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Ovary

3.1 - 7.4
CD-1 Ovary tumor Ovary

0
CD-1 Ovary tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Ovary

0 - 11.1
CD-1 Ovary tumor
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Ovary

0
CD-1 Ovary tumor
  • sodium barbital (BB)
 Ovary

0 - 5.0
CD-1 PNS - Schwann cell neurofibrosarcoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Leg

1.9
CD-1 Pancreas - Islet of Langerhans adenoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Pancreas - Islet of Langerhans

1.9
CD-1 Pancreas tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Pancreas

0.9
CD-1 Pituitary gland adenoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Pituitary gland

2.0
CD-1 Pituitary gland adenoma
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Pituitary gland

2.8
CD-1 Reproductive system (sex not specified) tumor Reproductive system (sex not specified)

3
CD-1 Reproductive system (sex not specified) tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Reproductive system (sex not specified)

7 - 12
CD-1 Seminal vesicle adenoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Seminal vesicle

3.6
CD-1 Seminal vesicle tumor Seminal vesicle

0
CD-1 Seminal vesicle tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Seminal vesicle

0 - 10.7
CD-1 Seminal vesicle tumor
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Seminal vesicle

0
CD-1 Seminal vesicle tumor
  • sodium barbital (BB)
 Seminal vesicle

0
CD-1 Skin - Epidermis - Basal cell tumor Skin - Epidermis - Basal cell

1.9
CD-1 Skin adenoma - sebaceous
  • 3'-azido-3'-deoxythymidine (AZT)
 Skin

1.9
CD-1 Skin keratoacanthoma
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Skin

2.7
CD-1 Skin papilloma
  • 3'-azido-3'-deoxythymidine (AZT)
 Skin

2.0
CD-1 Testis - Leydig cell (Interstitial cell) tumor Testis - Leydig cell (Interstitial cell)

0
CD-1 Testis - Leydig cell (Interstitial cell) tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Testis - Leydig cell (Interstitial cell)

0 - 15.4
CD-1 Testis - Leydig cell (Interstitial cell) tumor
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Testis - Leydig cell (Interstitial cell)

0
CD-1 Testis - Leydig cell (Interstitial cell) tumor
  • sodium barbital (BB)
 Testis - Leydig cell (Interstitial cell)

0 - 9.1
CD-1 Thyroid gland - Follicular cell adenoma
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Thyroid gland - Follicular cell

5.6
CD-1 Thyroid gland - Follicular cell adenoma
  • sodium barbital (BB)
 Thyroid gland - Follicular cell

5.7
CD-1 Thyroid gland - Medulla - C cell adenoma
  • 3'-azido-3'-deoxythymidine (AZT)
 Thyroid gland - Medulla - C cell

1.9
CD-1 Thyroid gland tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Thyroid gland

0.9
CD-1 Uterus - Cervix tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Uterus - Cervix

0 - 7.1
CD-1 Uterus polyp
  • 3'-azido-3'-deoxythymidine (AZT)
 Uterus

3.1 - 9.1
CD-1 Uterus tumor Uterus

0 - 13.0
CD-1 Uterus tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 Uterus

0 - 21.4
CD-1 Uterus tumor
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Uterus

0
CD-1 Uterus tumor
  • sodium barbital (BB)
 Uterus

0
CD-1 Vagina tumor - epithelial Vagina

0
CD-1 Vagina tumor - epithelial
  • 3'-azido-3'-deoxythymidine (AZT)
 Vagina

0
CD-1 Vagina tumor - epithelial
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 Vagina

0
CD-1 Vagina tumor - epithelial
  • sodium barbital (BB)
 Vagina

0
CD-1 (Unspecified organ) neoplasm
  • 3'-azido-3'-deoxythymidine (AZT)
 (Unspecified organ)

0 - 32.1
CD-1 (Unspecified organ) neoplasm
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 (Unspecified organ)

0 - 8.7
CD-1 (Unspecified organ) neoplasm (Unspecified organ)

0 - 3.2
CD-1 (Unspecified organ) neoplasm
  • sodium barbital (BB)
 (Unspecified organ)

0
CD-1 (Unspecified organ) tumor (Unspecified organ)

16.1 - 43.5
CD-1 (Unspecified organ) tumor
  • 3'-azido-3'-deoxythymidine (AZT)
 (Unspecified organ)

0 - 50
CD-1 (Unspecified organ) tumor
  • sodium barbital (BB)
  • 3'-azido-3'-deoxythymidine (AZT)
 (Unspecified organ)

7.7 - 52.2
CD-1 (Unspecified organ) tumor
  • sodium barbital (BB)
 (Unspecified organ)

0 - 45