title: Arsenic exposure in utero and nonepidermal proliferative response in adulthood in Tg.AC mice.
abstract: To expand our knowledge on the transplacental carcinogenic potential of inorganic arsenic, pregnant Tg.AC mice received drinking water with 0, 42.5, or 85 ppm arsenite from gestation day 8 to 18. After birth, groups (n = 25) of offspring received topical 12-O-tetradecanoyl phorbol-13-acetate (TPA) (2 microg twice a week) for 36 weeks and were killed; nonskin tumors were assessed. Arsenic increased adrenal cortical adenomas (ACAs; 25%-29%) compared with control (0%) independent of TPA in all male groups. Arsenic increased urinary bladder (UB) hyperplasia in males, but only with TPA. Arsenic induced ACAs in all female groups (control 0%; arsenic 17%-26%). Arsenic-treated females had UB hyperplasia in most groups (control 0%; arsenic 26%-32%), with 2 UB papillomas. All arsenic-treated females had uterine hyperplasia (26%-40%; control 4%) independent of TPA, and 3 had uterine tumors. Thus, arsenic in utero rapidly induces ACAs and uterine and UB preneoplasias in Tg.AC mice, showing transplacental carcinogenic potential in yet another strain of mice.
authors.affiliation: National Cancer Institute at NIEHS, 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: Michael P
authors.initials: MP
authors.lastname: Waalkes
mesh_terms: D000236:Adenoma / Q000139:chemically induced; D000306:Adrenal Cortex Neoplasms / Q000139:chemically induced; D000375:Aging; D000818:Animals; D001151:Arsenic / Q000008:administration & dosage / Q000633:toxicity*; D018053:Arsenites / Q000008:administration & dosage / Q000633:toxicity*; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects; D051379:Mice; D010212:Papilloma / Q000139:chemically induced; D011230:Precancerous Conditions / Q000139:chemically induced; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D012727:Sex Characteristics; D017670:Sodium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced; D014594:Uterine Neoplasms / Q000139:chemically induced
chemical_list: D018053:Arsenites; D002273:Carcinogens; D017670:Sodium Compounds; C017947:sodium arsenite; D001151:Arsenic; D013755:Tetradecanoylphorbol Acetate
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