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Query: UMLS:C0242379 (lung cancer)
 71,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We seek to create a canine lung cancer model with sharply localized carcinomas analogous to human lung cancers. Toward this goal techniques for recurrent endobronchial transbronchoscopic submucosal injections and topical applications of the carcinogens 3,4-benzo(a)pyrene and N-methyl-nitrosourea have been developed. After 2 years of experience with 2,868 endoscopic manipulations and varying dosage schedules in 59 dogs, safe effective techniques for recurrently delivering carcinogens and sequential biopsies of the same sites have evolved. Predominantly during the first year of experience, 10 dogs died as a consequence of technical problems such as exsanguinations after 1 mm. punch biopsies. There were also 39 instances of nonlethal technical complications of endoscopy in the face of immunosuppression and local irritation caused by the carcinogens. By the techniques and dosage schedules described, it has now become possible reliably and safely to create impressive localized bronchial preneoplasia with squamous metaplasia and atypia among the prominent features.
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PMID:Techniques for localized injections and topical applications of carcinogens at specific endobronchial sites in dogs. 83 62

This paper has reviewed the temporal and spatial distribution of lung cancer in the United States. Some of the personal characteristics which are important determinants of this type of cancer and which need to be considered in assessing the role of environmental air pollution have also been considered. Recent studies which have attempted to relate lung cancer mortality to possible arsenic exposure or to levels of benzo[a]pyrene in different places are noted. While an urban effect is undoubted, it is still not certain that it is due to carcinogenic pollutants in the air. Although there may be exceptional areas, environmental air pollution probably contributes only a very small fraction to the effect of cigarette smoking on this type of cancer.
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PMID:Epidemiology of lung cancer in the United States. 87 36

The effect of carrier particle size on the rate of dissociation of benzo[alpha]pyrene (BaP) from carrier particles deposited in the respiratory tract of mice was studied. BaP-coated carbon particles (in two size ranges, 0.5-1.0 and 15-30 mum) plus 103Ru-tagged carbon tracer particles were intratracheally instilled in mice. The clearance of carbon particles and the simultaneous rate of elimination of BaP from the respiratory tract was measured. BaP adsorbed to 15- to 30-muM carbon particles was eliminated from the lung at essentially the same rate as the carbon particles were cleared. In contrast, BaP adsorbed to 0.5- to 1.0-muM carbon particles was eliminated from the lung approximately 4 times faster than the carbon particles were cleared. The persistence of carcinogens and their rates of elution from carrier particles are discussed in relation to the pathogenesis of lung cancer in animals treated with carcinogen-carrier particle preparations.
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PMID:Elution of benzo[alpha]pyrene from carbon particles in the respiratory tract of mice. 96 24

Levels of activity of the enzyme aryl hydrocarbon hydroxylase and cytochrome P450 have been estimated in lung and liver of rats exposed to graded doses of cigarette smoke and in human bronchial mucosa of smokers, non-smokers and patients with lung cancer. Exposure of rats to smoke of four cigarettes increased both hepatic and pulmonary aryl hydrocarbon hydroxylase activity. Exposure to smoke of four cigarettes daily for seven and 14 days did not result in higher aryl hydrocarbon hydroxylase levels in the liver than one day's exposure, but in the lung longer exposures caused greater increases in enzyme activity. Injection of benzo(a)pyrene at two dose levels caused a much greater increase in both liver and lung aryl hydrocarbon hydroxylase than smoking. The lower dose maximally stimulated the enzyme in both organs. The changes in aryl hydrocarbon hydroxylase activity were accompanied by significant increases in both liver weight and the cytochrome P450 content of liver microsomes but the increase in cytochrome P450 did not parallel those in aryl hydrocarbon hydroxylase activity. Of 40 surgical and autopsy specimens of human lung and tracheal mucosa from smokers, non-smokers and cancer patients, only one was found to have detectable aryl hydrocarbon hydroxylase activity. The relationship between aryl hydrocarbon hydroxylase induction by cigarette smoke in human tissues and the development of bronchogenic carcinoma in smokers remains unclear.
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PMID:The effect of cigarette smoke on aryl hydrocarbon hydroxylase activity and cytochrome P450 content in rat liver and lung microsomes. 102 52

The studies reported here demonstrate some of the factors affecting the binding of benzo(a)pyrene (BP) to macromolecules in cultured human bronchial mucosa. Bronchial specimens were obtained at either surgy or "immediate" autopsy from patients with and without lung cancer. Grossly normal-appearing pieces of bronchus were cultured in a chemically defined medium, i.e., CMRL 1066 medium containing 1 mug insulin per ml, 0.1 mug beta-retinyl acetate per ml,, 0.1 mug hydrocortisone hemisuccinate per ml, 2 mM L-glutamine, 100 units penicillin G per ml, and 100 mug streptomycin per ml. After 7 days, explant cultures were exposed to [3H]BP, usually for 24 hr, and then binding to total cellular macromolecules was studied by autoradiography, and binding to DNA was measured following isolation of DNA from bronchial mucosal cells. The extent of binding of [3H]BP was dependent on dose of BP, length of exposure to [3H]BP, and temperature. By autoradiography, bronchial epithelial cells bound more [3H]BP than stromal fibroblasts. Both 7,8-benzoflavone and butylated hydroxytoluene appeared to reduce the level of [3H]BP bound to DNA, while nicotine apparently did not alter the level of binding. These studies demonstrate that the bronchial mucosa, an important human cancer target tissue, has the capability to form metabolites of BP which bind to macromolecules including DNA. In addition, 7,8-benzoflavone and butylated hydroxytoluene, both known to alter the microsomal metabolism of BP, reduce the level of [3H]BP bound to DNA.
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PMID:Binding of (3H)benzo(a)pyrene to DNA in cultured human bronchus. 2809 25

Quantitative criteria of the action of chemical carcinogenic compounds serve as the basis for establishing the degree of danger they pose and of safety levels. The presence of the tumor is proposed as a specific index of the harmfulness of carcinogenic action. There are no indices for determining the initial stages of the neoplastic process before the tumor appears. Both the frequency and the time required for development are important. A study was made of the carcinogenic activity of benz(a)pyrene on rats. The drug was given by intratracneal administration in doses of .005, .02, .01, .05, and 2.5 mg repeated 10 times over a 10-month period. A total dose of .1 mg was minimally effective. However, .02 mg benz(a)pyrene was selected as the minimum effective single dose amount for estimated time periods longer than the life span of the animals and of the comparative span of human life. Tumors were produced in the lungs and other organs of the rats. Histological types varied. The dose given had an effect on the histological type of lung cancer. Large doses tended to produce epidermoid cancer while lower doses produced mostly adenocarcinoma. Some types found have not been recorded as spontaneously occurring in rats. The number of tumor-bearing animals diminished as the dose was reduced and the time for appearance of tumors increased. The number of spontaneous tumors in control animals increased with time. Animal strains with a high cancer susceptibility are needed in testing the small doses of a carcinogen since spontaneous tumors are an indication of sensitivity to carcinogenic substances. However, random-bred animals have a closer approximation to the human population and may be better for some experiments. For the optimal experiment, administration of a carcinogen should be over the entire life span of the individual. Another procedure is by using different doses in a short-term experiment to obtain a dose-time effect. On the basis of data obtained, the maximum permissible concentration of benz(a)pyrene in the ambient air can be determined.
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PMID:Predicting the risk of tumor occurrence under the effect of small doses of carcinogens. 126 13

The first group of non-bred rats was injected intrapleurally 20 mg of benzene extracted chrysotil-asbestos dust in saline; the second group of rats was injected 20 mg of the same dust but with benz(a)pyrene absorbed on it (0.4 mg). Pleural mesotheliomas were observed in 48.57% of cases in the first group and in 41.37% of cases in the second one. The difference was not significant. There was no difference in the percentage of premesotheliomatous lesions. But, in the second group tumors of other organs were found. The role of asbestos pollution by carcinogenic hydrocarbons in the genesis of lung cancer and pleural mesothelioma is discussed.
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PMID:[Mechanism of the induction of asbestos mesotheliomas in the pleura of rats]. 127 66

Se-malt cakes containing 300 micrograms selenium were given daily to men from high risk area of lung cancer and the influence of ultraviolet light (UV) and be benzo(a)pyrene (B(a)P) induced unscheduled DNA synthesis (UDS) of peripheral lymphocytes were determined. After Se-supplementation for 6 months, the Se levels in serum, hairs and activity of GSH-px were increased by 89%, 67% and 178%, respectively. The ratio of UV-induced UDS was decreased from the mean value of 2.47 in the control to 1.61 (P < 0.05) in the Se-group. After Se-intake for one year, the Se levels were elevated by 78% in serum, 83% in hairs and 56% in GSH-px activity, while the mean value of B alpha P-induced UDS was reduced from 2.21 in the control to 1.47 (P < 0.05) in the Se-group. The results of the present study indicate a blocking effect of Se-supplementation to UV- and B alpha P-induced UDS of peripheral lymphocytes from high risk subjects for lung cancer.
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PMID:[Effects of Se-enriched malt cakes on UV benzo(a)pyrene induced unscheduled DNA synthesis of lymphocytes from high risk population of lung cancer]. 129 Dec 89

The in vitro formation of benzo[a]pyrene-DNA adducts was determined in peripheral blood monocytes of 22 lung cancer patients with at least one first-degree relative with lung cancer and compared to results obtained in 30 healthy controls. In patients, the mean (SEM) adduct formation was 2.8 (0.3) fmol/micrograms DNA as compared to 2.1 (0.1) fmol/micrograms in controls (p less than 0.05), and it was independent of age and smoking habits. These findings support the hypothesis that carcinogen-DNA adduct formation may be one factor of a constitutionally enhanced lung cancer risk.
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PMID:Formation of benzo[a]pyrene-DNA adducts in blood monocytes from lung cancer patients with a familial history of lung cancer. 130 33

Cigarette smoking is the strongest risk factor for lung cancer, but genetically determined variations in the activities of pulmonary enzyme that metabolize tobacco-derived carcinogens may affect individual risk. To investigate whether these enzymes (e.g., CYP1A-related) can serve as markers for carcinogen-DNA damage, lung tissue specimens were taken during surgery from middle-aged men with either lung cancer or non-neoplastic lung disease. Phase I [aryl hydrocarbon hydroxylase (AHH), ethoxycoumarin O-deethylase (ECOD)] and phase II (epoxide hydrolase, UDP-glucuronosyltransferase, glutathione S-transferase) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were also analyzed for DNA adducts, using 32P-postlabeling. The data were then analyzed for the following: a) differences in metabolic profiles between bronchial and parenchymal lung tissue; b) the effect of recent exposure to tobacco smoke on enzyme inducibility and benzo[a]pyrene metabolism; c) differences in enzyme inducibility between lung cancer and non-lung cancer patients; d) the effect of smoking on metabolism of mutagens in vitro; e) pulmonary DNA adduct levels and AHH activity in lung parenchyma of smokers and ex-smokers; f) lipid peroxidation products in lung tissue from lung cancer and non-lung cancer patients, as related to smoking habits and degree of airway obstruction; and g) prognostic value of AHH pulmonary activity in lung cancer patients. The results demonstrate a pronounced effect of tobacco smoke on pulmonary metabolism of xenobiotics and prooxidant state and suggest the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer.
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PMID:Carcinogen metabolism in human lung tissues and the effect of tobacco smoking: results from a case--control multicenter study on lung cancer patients. 133 22


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