Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Female Swiss mice were exposed to sodium arsenite or sodium aresenate in the drinking water for 15 weeks at concentrations ranging from 0 to 100 micrograms/mL arsenic content. After three weeks of the 15 week exposure period, the mice were administered urethan (1.5 mg/g) intraperitoneally. Pulmonary adenoma formation was evaluated 12 weeks later. Arsenic exposure produced a protective effect with respect to tumor development. Both forms of arsenic reduced the size and number of pulmonary adenomas observed per mouse. In addition, urethan-induced sleeping times which reflect the rate of urethan metabolism or excretion remained unchanged. This suggests that arsenic exposure does not alter urethan excretion and is not a factor influencing subsequent adenoma formation of these levels of exposure.
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PMID:The effect of arsenic on urethan-induced adenoma formation in Swiss mice. 360 54

Female Swiss were exposed to sodium selenite (3 micrograms/ml selenium content) and sodium arsenate (80 micrograms/ml arsenic content) in the drinking water individually or in combination on alternate days for 15 weeks. Comparable water consumption was observed in all individual or combined metal-exposure groups. After 3 weeks of metal exposure, the mice were administered urethan (1.5 mg/g) intraperitoneally. Pulmonary adenoma formation was evaluated 12 weeks later. Arsenic exposure reduced the tumor incidence (P = 0.0046) and tumor size (P less than 0.0001). Selenium exposure did not alter the tumor incidence but caused a reduction in tumor size (P = 0.022). No selenium-arsenic interactions associated with tumor size or number were observed. Urethan-induced sleeping times were unaffected by exposure to selenium (P = 0.832) or arsenic (P = 0.42), although combined metal exposure reduced the duration of urethan-induced sleep (P = 0.029) as compared to the individual metal exposures. This metal-metal interaction, which appeared to enhance the rate of urethan elimination as indicated by the reduced sleeping time, did not influence adenoma formation significantly.
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PMID:Alterations in urethan-induced adenoma formation in mice exposed to selenium and arsenic. 360 32

Pregnant CD1 mice received 85 ppm arsenite in the drinking water from gestation day 8 to 18, groups (n = 35) of male offspring were subsequently injected on postpartum days 1 through 5 with diethylstilbestrol (DES; 2 microg/pup/day) or tamoxifen (TAM; 10 microg/pup/day), and tumor formation was assessed over 90 weeks. Arsenic alone increased hepatocellular carcinoma (14%), adenoma (23%) and total tumors (31%) compared to control (0, 2 and 2%, respectively). Arsenic alone also increased lung adenocarcinoma, adrenal cortical adenoma and renal cystic tubular hyperplasia compared to control. Compared to arsenic alone, arsenic plus DES increased liver tumor incidence in mice at risk 2.2-fold and increased liver tumor multiplicity (tumors/liver) 1.8-fold. The treatments alone did not impact urinary bladder carcinogenesis, but arsenic plus TAM significantly increased formation of urinary bladder transitional cell tumors (papilloma and carcinoma; 13%) compared to control (0%). Urinary bladder proliferative lesions (combined tumors and hyperplasia) were also increased by arsenic plus TAM (40%) or arsenic plus DES (43%) compared to control (0%) or the treatments alone. Urinary bladder proliferative lesions occurred in the absence of any evidence of uroepithelial cytotoxic lesions. Urinary bladder lesions and hepatocellular carcinoma induced by arsenic plus TAM and/or DES overexpressed estrogen receptor-alpha, indicating that aberrant estrogen signaling may have been a factor in the enhanced carcinogenic response. Thus, in male CD1 mice, gestational arsenic exposure alone induced liver adenoma and carcinoma, lung adenocarcinoma, adrenal adenoma and renal cystic hyperplasia. Furthermore, DES enhanced transplacental arsenic-induced hepatocarcinogenesis. In utero arsenic also initiated urinary bladder tumor formation when followed by postnatal TAM and uroepithelial proliferative lesions when followed by TAM or DES.
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PMID:Enhanced urinary bladder and liver carcinogenesis in male CD1 mice exposed to transplacental inorganic arsenic and postnatal diethylstilbestrol or tamoxifen. 1671 94

Arsenic is a human pulmonary carcinogen. Our work indicates that in utero arsenic exposure in mice can induce or initiate lung cancer in female offspring. To define early molecular changes, pregnant C3H mice were given 85 ppm arsenic in drinking water from days 8 to 18 of gestation and expression of selected genes in the fetal lung or in lung tumors developing in adults was examined. Transplacental arsenic exposure increased estrogen receptor-alpha (ER-alpha) transcript and protein levels in the female fetal lung. An overexpression of various estrogen-regulated genes also occurred, including trefoil factor-3, anterior gradient-2, and the steroid metabolism genes 17-beta-hydroxysteroid dehydrogenase type 5 and aromatase. The insulin growth factor system, which can be influenced by ER and has been implicated in the pulmonary oncogenic process, was activated in fetal lung after gestational arsenic exposure. In utero arsenic exposure also induced overexpression of alpha-fetoprotein, epidermal growth factor receptor, L-myc, and metallothionein-1 in fetal lung, all of which are associated with lung cancer. Lung adenoma and adenocarcinoma from adult female mice exposed to arsenic in utero showed widespread, intense nuclear ER-alpha expression. In contrast, normal adult lung and diethylnitrosamine-induced lung adenocarcinoma showed little evidence of ER-alpha expression. Thus, transplacental arsenic exposure at a carcinogenic dose produced aberrant estrogen-linked pulmonary gene expression. ER-alpha activation was specifically associated with arsenic-induced lung adenocarcinoma and adenoma but not with nitrosamine-induced lung tumors. These data provide evidence that arsenic-induced aberrant ER signaling could disrupt early life stage genetic programing in the lung leading eventually to lung tumor formation much later in adulthood.
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PMID:Fetal onset of aberrant gene expression relevant to pulmonary carcinogenesis in lung adenocarcinoma development induced by in utero arsenic exposure. 1707 88

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).
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PMID:Lung tumors in mice induced by "whole-life" inorganic arsenic exposure at human-relevant doses. 2732 33