Carcinogenic Effects of “Whole-Life” Exposure to Inorganic Arsenic in CD1 Mice

• DOI: 10.1093/toxsci/kfq315
• Publication Date: 2010-10-18T21:38:07Z
• Authors: Erik J. Tokar; Bhalchandra A. Diwan; Jerrold M. Ward; Don A. Delker; Michael P. Waalkes
• Keywords: Transplacental; Arsenic toxicity

In a previously developed mouse model, arsenic exposure in utero induces tumors at multiple sites the offspring as adults, often duplicating human targets. However, environmental inorganic occurs during entire life span, not just part of gestation. Thus, "whole-life" carcinogenesis mice was studied. CD1 were exposed to 0, 6, 12, or 24 ppm drinking water 2 weeks prior breeding, pregnancy, lactation, and after weaning through adulthood. Tumors assessed until years age. Arsenic induced dose-related increases lung adenocarcinoma (both sexes), hepatocellular carcinoma gallbladder (males), uterine carcinomas. ovarian (including carcinomas) starting with lowest dose. Adrenal increased all doses sexes). Arsenic-induced liver cancers highly enriched for cancer stem cells, consistent work skin stimulated by prenatal arsenic. Reproductive tract overexpressed cyclooxygenase-2 estrogen receptor-α. target remarkably similar transplacental studies, although from whole-life generally more aggressive frequent. This may indicate that arsenic-induced events dictate site some tissues, whereas other periods enhance incidence progression, though factors could be play, like cumulative Whole-life dramatically lower external than only while realistically exposure.