title: 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.
authors.affiliation: Inorganic Toxicology Group, National Toxicology Program Laboratory Branch, Division of the National Toxicology Program, The National Institute of Environmental Health Sciences, 111 Alexander Drive, P.O. Box 12233, MD E1-07, Research Triangle Park, NC 27709, USA.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Tokar
authors.forename: Bhalchandra A
authors.initials: BA
authors.lastname: Diwan
authors.forename: David J
authors.initials: DJ
authors.lastname: Thomas
authors.forename: Michael P
authors.initials: MP
authors.lastname: Waalkes
mesh_terms: D000230:Adenocarcinoma / Q000139:chemically induced; D000236:Adenoma / Q000139:chemically induced; D000310:Adrenal Gland Neoplasms / Q000139:chemically induced; D000818:Animals; D001151:Arsenic / Q000008:administration & dosage / Q000633:toxicity*; D001152:Arsenicals / Q000009:adverse effects*; D002273:Carcinogens / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005260:Female; D008113:Liver Neoplasms / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D009369:Neoplasms / Q000139:chemically induced*; D010051:Ovarian Neoplasms / Q000139:chemically induced; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000209:etiology*; D011297:Prenatal Exposure Delayed Effects; D013736:Testicular Neoplasms / Q000139:chemically induced; D014594:Uterine Neoplasms / Q000139:chemically induced
chemical_list: D001152:Arsenicals; D002273:Carcinogens; C020300:monomethylarsonic acid; D001151:Arsenic