Arsenic exposure in utero and nonepidermal proliferative response in adulthood in Tg.AC mice.
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.
Tokar
Erik J
EJ
National Cancer Institute at NIEHS, Research Triangle Park, NC 27709, USA.
Diwan
Bhalchandra A
BA
Waalkes
Michael P
MP
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
D018053:Arsenites; D002273:Carcinogens; D017670:Sodium Compounds; C017947:sodium arsenite; D001151:Arsenic; D013755:Tetradecanoylphorbol Acetate
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