Abstract:
:The effects of oral contraceptives have been studied in the beagle bitch for periods up to 7 yr. High doses of these potent estrogen: progestogen (E:P) combinations have been shown to promote tumors in the mammary glands, smooth muscle of the tubular genitalia, and occasionally in the transitional epithelium of the neck/trigone area of the urinary bladder. The contraceptive formulations used in humans are balanced with an E:P ratio of about 1:5 to 1:80 to produce a desired decidual response in the uterus. The corresponding ratio for producing the decidual reaction in the dog is 1:1,000 to 1:3,000 with the result that the dog is grossly overdosed with estrogens when given the human formulation at the usual multiples of up to 25 times the human dose. Smooth muscle tumors of the tubular reproductive tract are common sequelae to estrogen overstimulation in the dog and are known to occur in other species, including the humans. The dog also has major differences in hormonal control and sensitivity when compared to humans. Progestogens stimulate synthesis and release of growth hormone (GH) in dogs which in turn is the major stimulant (with progestogens) of mammary growth and tumors. Evidence is accumulating which indicates that most if not all progestogens can produce mammary tumors in the dog if given by the correct route and at high enough dosage. In contrast, GH in humans is not increased nor does it have any significant mammotrophic role. Mammary tumors in dogs related to oral contraceptives are now widely considered to be irrelevant as a model or predictor for human tumors. Transitional cell tumors in the urinary bladder seem to be a species specific phenomenon seen on occasion in the dog, but not in the rat, monkey, or human. The usual location in the neck/trigone area may be related to the embryologic origin of this portion of the bladder, which derives from tissues more closely related to the genital organs than does the rest of the bladder.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Johnson ANdoi
10.1177/019262338901700216subject
Has Abstractpub_date
1989-01-01 00:00:00pages
389-95issue
2eissn
0192-6233issn
1533-1601journal_volume
17pub_type
杂志文章,评审abstract::The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak that started in Wuhan, China, in 2019 resulted in a pandemic not seen for a century, and there is an urgent need to develop safe and efficacious vaccines. The scientific community has made tremendous efforts to understand the disease, and unpara...
journal_title:Toxicologic pathology
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journal_title:Toxicologic pathology
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abstract::Seventeen mesotheliomas from 395 untreated male Fischer 344/DuCrj rats were studied by light and electron microscopy to define the morphological characteristics of the tumors. In 16 out of 17 rats, mesotheliomas were observed in the abdominal and/or scrotal sac, and the other one was localized on the pleura. Grossly, ...
journal_title:Toxicologic pathology
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abstract::Macrophages appearing in lesions are polarized toward M1 (for inflammation) and M2 (for anti-inflammation/fibrosis) types. We analyzed immunophenotypes of macrophages appearing in myocardial lesion in rats injected once with isoproterenol (10 mg/kg body weight). Inflammation following myocardial necrosis on day 1 was ...
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abstract::Dichloroacetic acid (DCA) and trichloroacetic acid (TCA) are metabolites of the industrial solvent and environmental contaminant trichloroethylene (TCE), as well as contaminants of chlorinated drinking water. Human exposure to these chemicals is of concern as all three have been shown to increase liver tumor incidence...
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abstract::Selenoprotein P is an abundant extracellular protein that is expressed in liver, brain, and other tissues. Studies in mice with the selenoprotein P gene deleted (Sepp-/- mice) have implicated the protein in maintaining brain selenium. Sepp-/- mice fed a normal or low selenium diet develop severe motor impairment and d...
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abstract::The performance of the p53-/- transgenic (knockout) mouse model was evaluated through review of the data from 31 short-term carcinogenicity studies with 21 compounds tested as part of the International Life Sciences Institute's (ILSI) Alternatives to Carcinogenicity Testing (ACT) project, together with data from other...
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journal_title:Toxicologic pathology
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journal_title:Toxicologic pathology
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journal_title:Toxicologic pathology
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doi:
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journal_title:Toxicologic pathology
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更新日期:1999-01-01 00:00:00
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journal_title:Toxicologic pathology
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journal_title:Toxicologic pathology
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journal_title:Toxicologic pathology
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abstract::Peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists such as fenofibrate are used to treat dyslipidemia. Although fenofibrate is considered safe in humans, it is known to cause hepatocarcinogenesis in rodents. To evaluate untargeted metabolic profiling as a tool for gaining insight into the underlying...
journal_title:Toxicologic pathology
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更新日期:2009-06-01 00:00:00