title: Lung tumors in mice induced by "whole-life" inorganic arsenic exposure at human-relevant doses.
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).
authors.affiliation: Inorganic Toxicology Group, National Toxicology Program Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, 111 Alexander Drive, MD E1-07, P.O. Box 12233, Research Triangle Park, NC, 27709, USA, waalkes@niehs.nih.gov.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Waalkes
authors.forename: Wei
authors.initials: W
authors.lastname: Qu
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Tokar
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kissling
authors.forename: Darlene
authors.initials: D
authors.lastname: Dixon
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D015197:Carcinogenicity Tests; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000473:pathology; D017670:Sodium Compounds / Q000633:toxicity*; D013045:Species Specificity; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D018053:Arsenites; D004785:Environmental Pollutants; D017670:Sodium Compounds; C017947:sodium arsenite