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PMID: 17306315 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Transplacental arsenic carcinogenesis in mice.

Toxicology and applied pharmacology ·Vol. 222 ·No. 3 ·2007-08-01 ·Pages 271-80

Waalkes MP, Liu J, Diwan BA

Abstract

Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show that a short period of maternal exposure to inorganic arsenic in the drinking water is an effective, multi-tissue carcinogen in the adult offspring. These studies have been reproduced in three temporally separate studies using two different mouse strains. In these studies pregnant mice were treated with drinking water containing sodium arsenite at up to 85 ppm arsenic from days 8 to 18 of gestation, and the offspring were observed for up to 2 years. The doses used in all these studies were well tolerated by both the dam and offspring. In C3H mice, two separate studies show male offspring exposed to arsenic in utero developed liver carcinoma and adrenal cortical adenoma in a dose-related fashion during adulthood. Prenatally exposed female C3H offspring show dose-related increases in ovarian tumors and lung carcinoma and in proliferative lesions (tumors plus preneoplastic hyperplasia) of the uterus and oviduct. In addition, prenatal arsenic plus postnatal exposure to the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) in C3H mice produces excess lung tumors in both sexes and liver tumors in females. Male CD1 mice treated with arsenic in utero develop tumors of the liver and adrenal and renal hyperplasia while females develop tumors of urogenital system, ovary, uterus and adrenal and hyperplasia of the oviduct. Additional postnatal treatment with diethylstilbestrol or tamoxifen after prenatal arsenic in CD1 mice induces urinary bladder transitional cell proliferative lesions, including carcinoma and papilloma, and enhances the carcinogenic response in the liver of both sexes. Overall this model has provided convincing evidence that arsenic is a transplacental carcinogen in mice with the ability to target tissues of potential human relevance, such as the urinary bladder, lung and liver. Transplacental carcinogenesis clearly occurs with other agents in humans and investigating a potential transplacental component of the human carcinogenic response to arsenic should be a research priority.

MeSH Terms
Animals Anticarcinogenic Agents/pharmacology Arsenic/toxicity Arsenicals/pharmacology Carcinogens/toxicity Carcinoma, Transitional Cell/chemically induced,pathology Data Interpretation, Statistical Diethylstilbestrol/toxicity Dose-Response Relationship, Drug Drug Synergism Estrogens/physiology,toxicity Female Gene Expression Regulation, Neoplastic/drug effects Male Maternal-Fetal Exchange/physiology Mice Mice, Inbred C3H Neoplasms/chemically induced,pathology Pregnancy Prenatal Exposure Delayed Effects Signal Transduction/drug effects Skin Neoplasms/chemically induced,pathology Tamoxifen/pharmacology Tetradecanoylphorbol Acetate/toxicity Urinary Bladder Neoplasms/chemically induced,pathology
Chemicals
Anticarcinogenic Agents Arsenicals Carcinogens Estrogens Tamoxifen Diethylstilbestrol Arsenic Tetradecanoylphorbol Acetate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Waalkes Michael P
Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. [email protected]
Liu Jie
Diwan Bhalchandra A
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Article Info
Journal
Toxicology and applied pharmacology
Abbr.
Toxicol Appl Pharmacol
ISSN
0041-008X
DOI
10.1016/j.taap.2006.12.034
Email
[email protected]
Published
2007-08-01
Epub
2007-00-12
Pages
271-80
Language
English
Region
United States
NLM ID
0416575
PMCID
PMC1995036
Subset
IM
Grants
NCI NIH HHS · N01CO12400 · United States
Intramural NIH HHS · Z01 BC005488-21 · United States
Intramural NIH HHS · Z99 ES999999 · United States
NCI NIH HHS · N01-CO-12400 · United States
External Links
PubMed source DOI: 10.1016/j.taap.2006.12.034 PMC Full Text View journal details
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