title: Impact of life stage and duration of exposure on arsenic-induced proliferative lesions and neoplasia in C3H mice.
abstract: Epidemiological studies suggest that chronic exposure to inorganic arsenic is associated with cancer of the skin, urinary bladder and lung as well as the kidney and liver. Previous experimental studies have demonstrated increased incidence of liver, lung, ovary, and uterine tumors in mice exposed to 85 ppm (approximately 8 mg/kg) inorganic arsenic during gestation. To further characterize age susceptibility to arsenic carcinogenesis we administered 85 ppm inorganic arsenic in drinking water to C3H mice during gestation, prior to pubescence and post-pubescence to compare proliferative lesion and tumor outcomes over a one-year exposure period. Inorganic arsenic significantly increased the incidence of hyperplasia in urinary bladder (48%) and oviduct (36%) in female mice exposed prior to pubescence (beginning on postnatal day 21 and extending through one year) compared to control mice (19 and 5%, respectively). Arsenic also increased the incidence of hyperplasia in urinary bladder (28%) of female mice continuously exposed to arsenic (beginning on gestation day 8 and extending though one year) compared to gestation only exposed mice (0%). In contrast, inorganic arsenic significantly decreased the incidence of tumors in liver (0%) and adrenal glands (0%) of male mice continuously exposed from gestation through one year, as compared to levels in control (30 and 65%, respectively) and gestation only (33 and 55%, respectively) exposed mice. Together, these results suggest that continuous inorganic arsenic exposure at 85 ppm from gestation through one year increases the incidence and severity of urogenital proliferative lesions in female mice and decreases the incidence of liver and adrenal tumors in male mice. The paradoxical nature of these effects may be related to altered lipid metabolism, the effective dose in each target organ, and/or the shorter one-year observational period.
authors.affiliation: United States Environmental Protection Agency, Office of Research and Development, National Health and Environmental Effects Research Laboratory, Research Triangle Park, NC, USA.
authors.forename: Gene J
authors.initials: GJ
authors.lastname: Ahlborn
authors.forename: Gail M
authors.initials: GM
authors.lastname: Nelson
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Grindstaff
authors.forename: Michael P
authors.initials: MP
authors.lastname: Waalkes
authors.forename: Bhalchandra A
authors.initials: BA
authors.lastname: Diwan
authors.forename: James W
authors.initials: JW
authors.lastname: Allen
authors.forename: Kirk T
authors.initials: KT
authors.lastname: Kitchin
authors.forename: R Julian
authors.initials: RJ
authors.lastname: Preston
authors.forename: Araceli
authors.initials: A
authors.lastname: Hernandez-Zavala
authors.forename: Blakely
authors.initials: B
authors.lastname: Adair
authors.forename: David J
authors.initials: DJ
authors.lastname: Thomas
authors.forename: Don A
authors.initials: DA
authors.lastname: Delker
mesh_terms: D000284:Administration, Oral; D000310:Adrenal Gland Neoplasms / Q000139:chemically induced* / Q000473:pathology; D000818:Animals; D018053:Arsenites / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004334:Drug Administration Schedule; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D018811:Maternal Exposure; D008431:Maternal-Fetal Exchange; D051379:Mice; D008809:Mice, Inbred C3H; D010057:Oviducts / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017670:Sodium Compounds / Q000633:toxicity*; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology; D014881:Water Supply
chemical_list: D018053:Arsenites; D002273:Carcinogens; D017670:Sodium Compounds; C017947:sodium arsenite