Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxymetholone has been identified as a suspected nongenotoxic carcinogen and has recently completed testing in a conventional National Toxicology Program (NTP) 2-yr rodent bioassay program. As a synthetic androgen with a limited historical database in toxicology, oxymetholone is an ideal candidate for prospective examination of the performance of short-term transgenic mouse models in the detection of carcinogenic activity. In the present series of 3 articles, studies are described where oxymetholone was evaluated prior to disclosure of the results of the NTP 2-yr bioassay. The accompanying articles provide evidence showing that oxymetholone is devoid of mutagenic activity yet elicits a positive carcinogenic response in the Tg.AC transgenic mouse model. In the present study, oxymetholone was administered by oral gavage to p53 heterozygous male and female mice for 26 wk at doses of 125, 625, and 1,250 mg/kg/day. The vehicle was 0.5% aqueous methylcellulose. Positive controls consisted of mice treated daily by oral gavage with 200 or 400 mg/kg/day of p-cresidine in corn oil. The oxymetholone-treated females showed significantly increased body weight gain and clitoral enlargement attributable to drug treatment. In addition, significant alterations in kidney, liver, and testis weights were attributable to oxymetholone. However, there were no neoplastic lesions that were attributable to oxymetholone in either sex. p-Cresidine produced unequivocal bladder neoplasms in both sexes at the high dose and in males at the lower dose. The absence of a neoplastic response with oxymetholone is consistent with the selectivity of the p53-/- mouse model for detecting carcinogens that act by genotoxic mechanisms.
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PMID:Oxymetholone: III. Evaluation in the p53+/- transgenic mouse model. 1052 29

Phenolphthalein (800 and 2400 mg/kg/day by gavage and 2400 mg/kg/day by diet) and bisacodyl (800-500, 4000-2000, and 8000 mg/kg/day by gavage) were administered to 15 male and 15 female and 20 male and 20 female p53(+/-) mice respectively for 26 weeks to investigate the potential carcinogenicity of each compound. Toxicokinetic analyses confirmed systemic exposure. p-Cresidine was administered by gavage (400 mg/kg/day) and served as the positive control agent in each study. Dietary phenolphthalein reduced survival in both sexes and early deaths were attributed to thymic lymphoma. No bisacodyl-related neoplasms were observed. Regardless of route of administration to p53(+/-) mice, phenolphthalein but not bisacodyl was unequivocally genotoxic, causing increased micronuclei in polychromatic erythrocytes. In the Syrian hamster embryo (SHE) cell transformation assay, phenolphthalein caused increases in morphologically transformed colonies, thereby corroborating NTP's earlier reports, showing phenolophthalein has potential carcinogenic activity. Bisacodyl was negative in the SHE assay. Results of these experiments confirm an earlier demonstration that dietary phenolphthalein causes thymic lymphoma in p53(+/-) mice and show that (1) phenolphthalein causes qualitatively identical results in this transgenic model regardless of route of oral administration, (2) phenolphthalein shows evidence of micronucleus induction in p53(+/-) mice for up to 26 weeks, (3) phenolphthalein induced transformations in the in vitro SHE assay, and (4) bisacodyl in p53(+/-) mice induces neither drug-related neoplasm, nor micronuclei in polychromatic erythrocytes, and did not induce transformations in the in vitro SHE assay.
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PMID:Phenolphthalein and bisacodyl: assessment of genotoxic and carcinogenic responses in heterozygous p53 (+/-) mice and syrian hamster embryo (SHE) assay. 1637 91

Epidemiologic data suggest that soy consumption may protect against cancer induction in several tissues in humans. Although the soy components responsible for this activity remain unidentified, isoflavones (e.g., genistein) and protease inhibitors (e.g., Bowman-Birk inhibitor complex [BBIC]) demonstrate chemopreventive activity in several animal cancer models. As part of their preclinical development for cancer prevention, PTI G-2535 (a soy isoflavone mixture containing 45% genistein, 23% daidzein, and 4% glycitein) and BBIC were evaluated for oncogenicity in p53((+/-)) mice. In separate studies, groups of 25 p53((+/-)) mice/sex received daily gavage exposure to PTI G-2535 (0, 250, 1000, or 2500 mg/kg/day) or BBIC (0, 500, 1000, or 2000 mg/kg/day) for 6 months. The high doses of both PTI G-2535 and BBIC were limited by viscosity. p-Cresidine (400 mg/kg/day) served as a positive-control article in both studies. PTI G-2535 induced no gross toxicity in any animal, but did induce a dose-related suppression of body weight gain in male mice. Modest hematologic alterations and increased liver and spleen weights were seen in both sexes exposed to the isoflavone mixture. BBIC had no significant effect on body weight, food consumption, clinical pathology, or organ weights in either sex. Histopathologic evaluations demonstrated no increases in the incidence of either benign or malignant tumors in any group of p53((+/-)) mice exposed to PTI G-2535 or to BBIC. By contrast, the positive-control article, p-cresidine, induced urinary bladder cancers in both studies. Neither PTI G-2535 nor BBIC demonstrates any evidence of oncogenicity in the p53((+/-)) mouse model.
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PMID:Oncogenicity evaluations of chemopreventive soy components in p53((+/-)) (p53 knockout) mice. 1671 37