Abstract:
:The lung is a target organ for the toxic effects of several chemical agents, including natural products, industrial chemicals, pesticides, environmental agents, and occasionally, drugs. Factors that establish the lung as a target organ include selective tissue exposure, high tissue oxygenation, and the presence of bioactivating systems that can generate toxic products from initially innocuous substances. Selective pulmonary exposure most often results from the fact that the lung serves as the major portal of entry for most airborne substances, but in some cases, selective exposure is the consequence of accumulation of agents, such as certain basic amines, from the circulation. Lung tumor development following long-term exposure to cigarette smoke or diesel engine exhaust is an example of pulmonary toxicity resulting from selective external exposure. Selective internal exposure, on the other hand, is exemplified by the pulmonary uptake of the herbicide paraquat from the circulation which is in part responsible for its lung-toxic effects. Although the lung contains drug metabolizing enzymes similar to those found in the liver, the enzymatic systems in the lung are sometimes highly concentrated in specific cell types. In the rabbit, for example, the lung-selective toxicity of the natural product ipomeanol is the consequence of relatively large amounts of cytochromes P450 2B1 and 4B1 in nonciliated bronchiolar epithelial cells (Clara cells) of the terminal airways. These P450 enzymes are highly proficient in vitro at converting ipomeanol to reactive products. Lung tissue contains other enzymic systems which are capable of catalyzing phase I biostransformation pathways (e.g., flavin-containing amine monooxygenase, amine oxidase, and prostaglandin synthase). Examples, however, where pulmonary metabolism by these pathways results in lung toxicity are less numerous than with P450 mediated reactions. Pulmonary prostaglandin H-synthase mediated cooxygenation has been shown to activate procarcinogens such as benzo(a)pyrene 7,8-dihydrodiol, aflatoxin B1, and monosubstituted hydrazines. The activities of pulmonary phase II (conjugation) pathways may also contribute to lung toxicity. Low glutathione transferase activity (relative to P450 mediated aryl hydrocarbon hydroxylase activity) in lung tissue has been suggested to correlate with elevated risk of lung cancer in smokers. Other examples of lung-specific toxic agents and possible causative roles of biotransformation are also discussed.
journal_name
Toxicol Patholjournal_title
Toxicologic pathologyauthors
Smith BR,Brian WRdoi
10.1177/019262339101900415subject
Has Abstractpub_date
1991-01-01 00:00:00pages
470-81issue
4 Pt 1eissn
0192-6233issn
1533-1601journal_volume
19pub_type
杂志文章,评审abstract::Previous work in our laboratory revealed that the pubertal period of reproductive development in the male rat was particularly vulnerable to gossypol exposure, with a higher frequency of round structures in the lumen of the cauda epididymidis in the treated rats. Herein, we utilized hemicastration and electron microsc...
journal_title:Toxicologic pathology
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abstract::The common marmoset, Callithrix jacchus, is the smallest nonhuman primate commonly used in biomedical research. Marmoset characteristics and propensities have enabled them to be used in a wide range of research as a model of human disease, physiology, drug metabolism, general toxicology, and reproductive biology. This...
journal_title:Toxicologic pathology
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abstract::Single doses of aspirin induce scattered foci of necrosis of proximal tubules in some strains of rats, whereas acute or sub-acute administration of phenylbutazone causes renal papillary necrosis. Initially, using Sprague-Dawley rats of CFY and CD strains, it became clear that these rats were not as susceptible to thes...
journal_title:Toxicologic pathology
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doi:10.1177/019262338601400214
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abstract::The B6C3F1 strain of mice is prone to develop liver nodules as animals grow older. This spontaneous tumor development is enhanced by dietary lipotrope deficiency. The present studies were performed to evaluate the liver of the B6C3F1 mice in early periods of lipotrope deficiency and before the nodules appear. Mice wer...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262338501300103
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abstract::Chronic (24-month) inhalation exposure to 5 or 10 ppm allyl glycidyl ether (AGE) induced nasal lesions in Osborne-Mendel rats and B6C3F1 mice. Inflammation, degeneration, regeneration, metaplasia, hyperplasia, and neoplasia were observed in the nasal mucosa. Squamous metaplasia and hyperplasia of the respiratory epith...
journal_title:Toxicologic pathology
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abstract::Documentation of Chinese materia medica (CMM) dates back to around 1,100 BC when only dozens of drugs were first described. By the end of the 16th century, the number of drugs documented had reached close to 1,900. And by the end of the last century, published records of CMM have reached 12,800 drugs. The recorded tra...
journal_title:Toxicologic pathology
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journal_title:Toxicologic pathology
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abstract::The carcinogenic potential of misoprostol, a synthetic prostaglandin E1 analogue with anti-ulcer potential, was evaluated in CD Sprague-Dawley rats. The compound was given daily by gavage at 24, 240, and 2,400 micrograms/kg, up to 150 times the daily human dose for 2 years. Necropsies were done on all animals and the ...
journal_title:Toxicologic pathology
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doi:10.1177/019262338701500201
更新日期:1987-01-01 00:00:00
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journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
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更新日期:1998-11-01 00:00:00
abstract::Morphologic lesions have received only limited attention as in vitro endpoints of toxicity. In the present work, "tissue" and cell morphology of control and toxicant-treated primary dissociated cerebrocortical cell cultures from fetal mice were examined using phase-contrast and bright-field microscopy. In untreated co...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/019262339302100506
更新日期:1993-09-01 00:00:00
abstract::Mer proto-oncogene tyrosine kinase (MerTK), which is expressed in the retinal pigment epithelium (RPE), regulates phagocytosis of shed photoreceptor outer segments (POS). To investigate the effects of drug-induced MerTK inhibition on the retina, UNC569, a specific MerTK inhibitor, was orally administered to male mice ...
journal_title:Toxicologic pathology
pub_type: 杂志文章
doi:10.1177/0192623317749469
更新日期:2018-02-01 00:00:00
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journal_title:Toxicologic pathology
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abstract::The dose dependence of L-ascorbic acid (AsA) copromotion of urinary bladder carcinogenesis with continuous concomitant administration of NaHCO3 was investigated. In the first experiment, 83 male F344 rats were all given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 wk and then divided into 5 groups, which re...
journal_title:Toxicologic pathology
pub_type: 杂志文章
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abstract::Enzyme histochemistry was assessed in semi-thin glycolmethacrylate sections after 100 mg/kg 2-bromoethanamine (BEA) hydrobromide had been given ip to male Wistar rats to induce renal papillary necrosis. Changes in the proximal tubular marker enzymes alkaline phosphatase (Alk Phos), gamma-glutamytranspeptidase (GGT) an...
journal_title:Toxicologic pathology
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journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
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更新日期:1989-01-01 00:00:00
abstract::The Tg.AC mouse is being evaluated for use in short-term carcinogenicity bioassays. Because the dermal test protocol necessitates dissolving test agents we determined the effects of several solvents on responsiveness of hemizygous mice to dermal applications of the classical skin tumor promoter. phorbol 12-myristate 1...
journal_title:Toxicologic pathology
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journal_title:Toxicologic pathology
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doi:10.1177/019262339802600216
更新日期:1998-03-01 00:00:00
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journal_title:Toxicologic pathology
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更新日期:1995-05-01 00:00:00
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journal_title:Toxicologic pathology
pub_type: 杂志文章,评审
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更新日期:2002-01-01 00:00:00
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journal_title:Toxicologic pathology
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更新日期:2014-01-01 00:00:00
abstract::Vaginal exfoliative cytology is commonly used in biomedical and toxicological research to classify the stages of the rodent estrous cycle. However, mouse vaginal exfoliative cytology is commonly used as a stand-alone tool and has not been evaluated in reference to vaginal histology and serum sex hormone levels. In thi...
journal_title:Toxicologic pathology
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abstract::In standard toxicity studies, the cardiac conduction tissue is not systematically sampled and examined for histopathological changes. Most methods described use serial sectioning perpendicular to the long axis of the sinoauricular node (SAN) and atrioventricular node (AVN). Dozens of slides are needed to allow examina...
journal_title:Toxicologic pathology
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更新日期:1995-01-01 00:00:00
abstract::Pepsinogens are acid protease enzymes of pepsin usually found in gastric mucosa. In the present study, we demonstrated the presence of pepsinogen isozymes in male Syrian golden hamster lung tissues by a combined immunohistochemical and biochemical approach. Immunohistochemically, using rat pepsinogen 1 antibody, pepsi...
journal_title:Toxicologic pathology
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更新日期:1991-01-01 00:00:00
abstract::Nephrotoxic renal injury, and especially drug nephrotoxicity is now a common cause of acute renal failure. The most common patterns of renal injury produced by nephrotoxins, tubular damage, and interstitial nephritis, are discussed here. Toxic agents which are primarily tubular toxins include certain antibiotics, cisp...
journal_title:Toxicologic pathology
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abstract::Successful development and use of biomarkers will improve the productivity of oncology drug development. Recognition of the importance of biomarkers for speeding drug development is reflected in the precise definitions and concepts proposed by an NIH Working Group to standardize terminology and promote a more coherent...
journal_title:Toxicologic pathology
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abstract::Helicobacter hepaticus infection induces sustained inflammation and carcinoma of the liver in A/JCr mice, and serves as a model of human cancers associated with viral hepatitis and H. pylorichronic gastritis. Here we describe the pathogenesis of premalignant disease in A/JCr mice infected with H. hepaticus. We inocula...
journal_title:Toxicologic pathology
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abstract::Toxicology of the male reproductive system has received increased interest in recent years partly fuelled by the growing reports of falling sperm counts and rising reproductive disorders in the human population. Recently revised regulatory guidelines for the safety assessment of pharmaceuticals and chemicals on reprod...
journal_title:Toxicologic pathology
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更新日期:1997-03-01 00:00:00