Summary
This study investigated whether lifetime exposure to inorganic arsenic at levels relevant to human exposure could cause cancer in mice. Male and female mice were exposed to 0, 50, 500, or 5,000 parts per billion (ppb) arsenic in drinking water starting before breeding and continuing through pregnancy, lactation, and the offspring’s entire lifespan (up to 2 years). The exposure did not affect maternal health, litter size, or offspring growth. However, mice exposed to 50 and 500 ppb arsenic showed significantly higher rates of lung tumors, including adenomas and carcinomas, compared with controls. Male offspring had particularly high tumor incidence, and female offspring also showed increased lung adenomas at 50 ppb. Overall, the findings suggest that long-term arsenic exposure at doses comparable to some human environmental exposures may increase lung tumor risk in mice.
PMID: 25005685
PMCID: PMC4130362
DOI: 10.1007/s00204-014-1305-8
Abstract
In mice, inorganic arsenic in the drinking water in the parts per million range via the dam during in utero life or with whole-life exposure is a multi-site carcinogen in the offspring. However, human arsenic exposure is typically in the parts per billion (ppb) range. Thus, we studied "whole-life" inorganic arsenic carcinogenesis in mice at levels more relevant to humans. Breeder male and female CD1 mice were exposed to 0, 50, 500 or 5,000 ppb arsenic (as sodium arsenite) in the drinking water for 3 weeks prior to breeding, during pregnancy and lactation, and after weaning (at week 3) groups of male and female offspring (initial n = 40) were exposed for up to 2 years. Tumors were assessed in these offspring. Arsenic exposure had no effect on pregnant dam weights or water consumption, litter size, offspring birthweight or weight at weaning compared to control. In male offspring mice, arsenic exposure increased (p < 0.05) bronchiolo-alveolar tumor (adenoma or carcinoma) incidence at 50-ppb group (51 %) and 500-ppb group (54 %), but not at 5,000-ppb group (28 %) compared to control (22 %). These arsenic-induced bronchiolo-alveolar tumors included increased (p < 0.05) carcinoma at 50-ppb group (27 %) compared to controls (8 %). An increase (p < 0.05) in lung adenoma (25 %) in the 50-ppb group compared to control (11 %) occurred in female offspring. Thus, in CD1 mice whole-life arsenic exposure induced lung tumors at human-relevant doses (i.e., 50 and 500 ppb).