Tumors and proliferative lesions in adult offspring after maternal exposure to methylarsonous acid during gestation in CD1 mice
- PMID: 22398986
- PMCID: PMC3459060
- DOI: 10.1007/s00204-012-0820-8
Tumors and proliferative lesions in adult offspring after maternal exposure to methylarsonous acid during gestation in CD1 mice
Abstract
Developmental exposure to inorganic arsenic is carcinogenic in humans and mice, and adult offspring of mice exposed to inorganic arsenic can develop tumors of the lung, liver, adrenal, uterus, and ovary. It has been suggested that methylarsonous acid (MMA3+), a product of the biological methylation of inorganic arsenic, could be a key carcinogenic species. Thus, pregnant CD1 mice were provided drinking water containing MMA3+ at 0 (control), 12.5, or 25 parts per million (ppm) from gestational days 8 to 18. Tumors were assessed in groups of male or female (initial n = 25) offspring up to 2 years of age. In utero treatment had no effect on survival or body weights. Female offspring exhibited increases in total epithelial uterine tumors (control 0%; 12.5 ppm 26%; 25 ppm 30%), oviduct hyperplasia (control 4%; 12.5 ppm 35%; 25 ppm 43%), adrenal cortical adenoma at 25 ppm (control 0%; 12.5 ppm 9%; 25 ppm 26%), and total epithelial ovarian tumors (control 0%; 12.5 ppm 39%; 25 ppm 26%). Male offspring showed dose-related increases in hepatocellular carcinoma (control 0%; 12.5 ppm 12%; 25 ppm 22%), adrenal adenoma (control 0%; 12.5 ppm 28%; 25 ppm 17%), and lung adenocarcinoma (control 17%; 12.5 ppm 44%). Male offspring had unusual testicular lesions, including two rete testis carcinomas, two adenomas, and three interstitial cell tumors. Overall, maternal consumption of MMA3+ during pregnancy in CD1 mice produced some similar proliferative lesions as gestationally applied inorganic arsenic in the offspring during adulthood.
Similar articles
-
Transplacental arsenic carcinogenesis in mice.Toxicol Appl Pharmacol. 2007 Aug 1;222(3):271-80. doi: 10.1016/j.taap.2006.12.034. Epub 2007 Jan 12. Toxicol Appl Pharmacol. 2007. PMID: 17306315 Free PMC article.
-
Transplacental carcinogenicity of inorganic arsenic in the drinking water: induction of hepatic, ovarian, pulmonary, and adrenal tumors in mice.Toxicol Appl Pharmacol. 2003 Jan 1;186(1):7-17. doi: 10.1016/s0041-008x(02)00022-4. Toxicol Appl Pharmacol. 2003. PMID: 12583988
-
Arsenic exposure in utero and nonepidermal proliferative response in adulthood in Tg.AC mice.Int J Toxicol. 2010 May-Jun;29(3):291-6. doi: 10.1177/1091581810362804. Int J Toxicol. 2010. PMID: 20448261 Free PMC article.
-
Toxicology and carcinogenesis studies of milk thistle extract (CAS No. 84604-20-6) in F344/N rats and B6C3F1 mice (Feed Studies).Natl Toxicol Program Tech Rep Ser. 2011 May;(565):1-177. Natl Toxicol Program Tech Rep Ser. 2011. PMID: 21685957 Review.
-
[Exploration of Epigenetic Changes and DNA Methylation Markers Associated with Liver Tumors Induced by Inorganic Arsenite Exposure in Mice].Nihon Eiseigaku Zasshi. 2015;70(3):181-5. doi: 10.1265/jjh.70.181. Nihon Eiseigaku Zasshi. 2015. PMID: 26411935 Review. Japanese.
Cited by
-
In utero arsenic exposure increases DNA damage and gene expression changes in umbilical cord mesenchymal stem cells (UC-MSCs) from newborns as well as in UC-MSC differentiated hepatocytes.Toxicol Rep. 2022 Sep 7;9:1728-1741. doi: 10.1016/j.toxrep.2022.09.002. eCollection 2022. Toxicol Rep. 2022. PMID: 36518486 Free PMC article.
-
Origins, fate, and actions of methylated trivalent metabolites of inorganic arsenic: progress and prospects.Arch Toxicol. 2021 May;95(5):1547-1572. doi: 10.1007/s00204-021-03028-w. Epub 2021 Mar 26. Arch Toxicol. 2021. PMID: 33768354 Free PMC article. Review.
-
Transplacental arsenic exposure produced 5-methylcytosine methylation changes and aberrant microRNA expressions in livers of male fetal mice.Toxicology. 2020 Apr 15;435:152409. doi: 10.1016/j.tox.2020.152409. Epub 2020 Feb 14. Toxicology. 2020. PMID: 32068019 Free PMC article.
-
Concordance between sites of tumor development in humans and in experimental animals for 111 agents that are carcinogenic to humans.J Toxicol Environ Health B Crit Rev. 2019;22(7-8):203-236. doi: 10.1080/10937404.2019.1642586. J Toxicol Environ Health B Crit Rev. 2019. PMID: 31795923 Free PMC article. Review.
-
Exposure to arsenic in utero is associated with various types of DNA damage and micronuclei in newborns: a birth cohort study.Environ Health. 2019 Jun 7;18(1):51. doi: 10.1186/s12940-019-0481-7. Environ Health. 2019. PMID: 31174534 Free PMC article.
References
-
- Chen Y, O’Brien T, Del Razo LM, et al. Tissue levels of arsenicals and skin tumor response following administration of monomethylarsonous acid and arsenite to K6/ODC mice. J Environ Pathol Toxicol Oncol. 2008;27:43–52. - PubMed
-
- Cohen SM, Ohnishi T, Arnold LL, et al. Arsenic-induced bladder cancer in an animal model. Toxicol Appl Pharmacol. 2007;222:258–263. - PubMed
-
- Eblin KE, Bredfeldt TG, Gandolfi AJ. Immortalized human urothelial cells as a model of arsenic-induced bladder cancer. Toxicology. 2008;248:67–76. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical