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

Air pollution often is suggested as being partly responsible for an increased incidence of lung cancer in cities. A problem with epidemiological studies is that the comparatively-small effect of air pollution is difficult to identify in the presence of larger and variable effects of cigarette smoking and other factors. This article describes an alternative approach to the estimation of cases of lung cancer that may be a result of air pollution. The concentration of a number of carcinogenic polycyclic aromatic hydrocarbons has been measured at two sites in Sydney and the relative contributions from various pollutant sources have been deduced. By means of a source inventory and an atmospheric dispersion model, concentrations have been derived for the whole Sydney region. Lung-cancer induction is calculated from the population that is exposed and the concentration of benzo(a)pyrene, which is used as a surrogate for the carcinogenic products of incomplete combustion. For the Sydney region, it is estimated that about 30 lung cancers a year could arise from polycyclic aromatic hydrocarbons in the ambient air.
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PMID:The risk of lung cancer from polycyclic aromatic hydrocarbons in Sydney air. 320 Jan 87

The activities of aryl hydrocarbon hydroxylase (AHH) and glutathione s-transferase (GST) were measured in the lung tissues of lung cancer patients and patients without lung cancer. The results indicate that after controlling for age, sex, smoking, living conditions, occupational exposure, and medication history, the ratio of AHH to GST (AHH/GST) in the lung tissues of cancer patients was significantly higher than that in noncancer patients. This difference might suggest a genetic difference in benzo[a]pyrene (BP) activations between the two groups of patients, but whether there is a casual relation between AHH/GST and lung cancer is still a question. AHH/GST was high in patients who smoked. It is conceivable that smoking might increase the rate of BP activation. There was a positive correlation between AHH activity and the amount the lung cancer patients smoked, but the AHH activity was not affected by smoking in noncancer patients. The AHH activity of lung cancer patients seems more sensitive to induction by polycyclic aromatic hydrocarbons than that of noncancer patients. However, this suggestion should be further verified.
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PMID:Correlation between lung cancer prevalence and activities of aryl hydrocarbon hydroxylase and glutathione S-transferase in human lung tissues. 327 May 15

Formation of DNA adducts and of water-soluble metabolites was studied in monocytes of 86 first-degree relatives of 15 families. Tests were performed with blood monocytes using (G-3H)-benzo[a]pyrene as a model pro-carcinogen. Variance analysis revealed significantly higher inter-familial than intra-familial variations. From these data we conclude that the formation of DNA adducts is genetically controlled. Therefore the enhanced formation of benzo[a]pyrene DNA adducts in lung cancer patients found in earlier studies may reflect a genetic predisposition for lung cancer in some patients.
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PMID:Formation of DNA adducts and water-soluble metabolites of benzo[a]pyrene in human monocytes is genetically controlled. 333 69

The S-12 fractions of lung peripheral parenchyma obtained from 80 male individuals, aged 17-71 years, were assayed as blind samples for the ability either to convert promutagens into bacterial mutagens or to decrease the potency of direct-acting mutagens in the Ames reversion test. In this system, lung preparations were completely ineffective in activating an N-nitroso compound (i.e., N-nitrosomorpholine) and polycyclic aromatic hydrocarbons [i.e., 3-methylcholanthrene and benzo(a)pyrene] or their metabolites [i.e., 3-hydroxy-benzo(a)pyrene and benzo(a)pyrene-trans-7,8-diol]. They yielded a borderline and sporadic activation of a cigarette smoke condensate, and a weak but frequent activation of an aromatic amine (i.e., 2-aminofluorene), of a heterocyclic amine (i.e., 2-amino-3,4-dimethylimidazo[4,5-f] and of a diamide (i.e., cyclophosphamide). The pulmonary metabolism was more oriented in the sense of detoxification, as shown by the consistent decrease of potency of direct-acting mutagens, including a metal (i.e., sodium dichromate), an acridine and nitrogen mustard derivative (i.e., 2-methoxy-6-chloro-9-[3-(2-chloromethyl)aminopropylamino]acridine or ICR 191), an epoxide (i.e., epichlorohydrin) and an N-oxide (i.e., 4-nitroquinoline-N-oxide). As assessed by means of a numerical score quantifying the variation of mutagenicity, a marked interindividual variability (up to 20-fold) was detected in the ability of lung specimens to affect the mutagenicity of test compounds. Such variability was not significantly related to the protein concentration of S-12 fractions, nor to the age of the patients under scrutiny, who during hospitalization were on normal institutional diets and did not receive any special drug treatment. The only significant difference between 20 noncancer and 60 lung cancer patients, irrespective of the histological type, was a decreased activation of cyclophosphamide in the latter group. Probably due to the high prevalence of smokers among lung cancer patients, a significantly decreased activation of cyclophosphamide was also observed in the group of smokers. Smoking habits were associated with a stimulation of detoxifying mechanisms which, in agreement with the results of a previous study with human alveolar macrophages (F. L. Petrilli et al., J. Clin. Invest., 77:1917-1924, 1986), was significant in the case of sodium dichromate. Such effect was further enhanced by considering only individuals smoking during the last 24 h before collecting lung specimens, and under these conditions it became significant also for ICR 191.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pulmonary metabolism of mutagens and its relationship with lung cancer and smoking habits. 362 Nov 72

Previous studies of chemical carcinogenesis in the lung of Syrian golden hamsters have utilized outbred (nonsyngeneic) animals. Using the endobronchial sustained release implant technique, which causes focally originating cancers in outbred hamsters, we studied the course of bronchial carcinogenesis in two varieties of syngeneic Syrian golden hamsters, the LSH and the F1D strains (BIO 15.16 male X BIO 87.20 female). With either 10% benzo(a)pyrene or 10% methylcholanthrene sustained release implants the time course of epithelial transition from normal to neoplastic was the same for F1D hamsters as previously described for outbred hamsters. Using 10% benzo(a)pyrene sustained release implants the incidence of cancers as a function of time was significantly lower (P less than 0.001) in LSH hamsters as compared to outbred and F1D animals. Of 19 tumors transplanted into syngeneic F1D hamsters, 16 have been successfully propagated by serial transplantation. We conclude that (a) F1D hamsters are comparable to outbred animals in the response of their bronchial epithelium to endobronchial benzo(a)pyrene and methylcholanthrene, (b) there are significant differences in susceptibility to bronchial chemical carcinogenesis among hamster strains, thereby giving opportunity to study potential genetic control mechanisms during bronchial carcinogenesis, and (c) F1D hamsters are suitable for studies of lung cancer biology using tumor transplantation methods.
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PMID:Differential susceptibility to bronchial carcinogenesis in syngeneic hamsters. 362 Dec 6

This study was performed to determine whether lymphocytes from individuals with lung cancer were more likely to bind benzo[a]pyrene (BP) metabolites in an in vitro test. The in vitro system consisted of peripheral blood lymphocytes incubated with increasing concentrations of [3H] benzo[a]pyrene in the presence of beta-naphthoflavone-induced rat liver microsomes and a NADPH-generating system. The radioactivity bound to a TCA-precipitate of the lymphocytes was determined. The apparent affinity (Km) and maximal binding (Vmax) of this binding were calculated from double reciprocal plots of the data. Seven patients with primary lung cancer (squamous cell carcinoma and undifferentiated small cell carcinoma), none of whom had smoked for at least 2 months, were studied as were 10 lung cancer free smokers, and the results compared with 13 age- and sex-matched controls. In lymphocytes from patients with primary lung cancer, Vmax of radiolabel bound to TCA-precipitable material was almost double that of non-smoking controls (205 +/- 19.2 pmol X 2h X 10(6) cells vs. 121 +/- 10.8 pmol X 2h X 10(6) cells, mean +/- S.E.M., P less than 0.01). Among individuals without lung cancer, smokers did not differ from non-smokers. In addition, there was no difference in Km of radiolabel binding to lymphocytes from patients in all 3 groups. It is concluded that binding of carcinogenic metabolites to cell components is increased in patients with lung cancer. Further studies are required to determine whether this increased binding is related to individual susceptibility of some smokers to lung cancer.
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PMID:Increased binding of benzo[a]pyrene metabolites to lymphocytes from patients with lung cancer. 369 47

Increased mortality due to various malignancies is reported from long-term exposed, non-ferrous smelter workers. In the present study the post-mortem distribution of cadmium, lead and zinc in lung, liver and kidney is reported and related to exposure and mortality. The study involved 86 male copper smelter workers who died after April 1975. Lung samples were taken from all workers and liver and kidney samples were taken from about one-quarter of the workers. Two control groups were used. The exposed workers were divided into six groups based upon diagnoses in medical records and autopsy protocols. Lead and zinc were analyzed by atomic absorption spectrophotometry and cadmium by neutron activation analysis. For the skewly distributed tissue levels, non-parametric statistical processing was used. Of the workers, 53% died from cardiovascular diseases and 30% from malignancies (8% from lung cancer). Cardiovascular diseases predominated in the two control groups: about 75 and 100%, respectively. Lung and liver cadmium concentrations were significantly higher in the lung cancer group of smelter workers than in the other groups of smelter workers (p less than 0.05) and rural controls (p less than 0.01). Cadmium in kidney, and lead in lung and liver were significantly higher (p less than 0.03) in the lung cancer group than in rural controls, but did not differ from that of the other workers. Zinc in lung, liver and kidney did not differ between exposed workers and controls. Rather strong Spearman rank-order correlation coefficients were found between the cadmium content of lung, liver and kidney tissue, especially in non-smoking smelter workers and rural controls. Smoking was more common in the lung cancer group than in the total group of smelter workers. Cadmium levels in the lungs of exposed workers were significantly higher (p less than 0.001) in smokers than in both ex-smokers and non-smokers. Earlier studies of the same workers gave significantly lower selenium levels in lung tissue compared with other groups of smelter workers and controls. As other carcinogenic substances are present in the working environment, e.g. arsenic, chromium and benzo [alpha]-pyrene, the specific effect of cadmium in the development of lung cancer cannot be evaluated at present.
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PMID:Distribution of cadmium, lead and zinc in lung, liver and kidney in long-term exposed smelter workers. 370 26

Workers in coke oven plants have a higher incidence of lung cancer than the general population. They are exposed to a variety of chemicals, in particular the polycyclic aromatic hydrocarbons (PAH), including benzo(a)pyrene. To evaluate the genotoxic effects of PAH exposure, air samples and urine samples were analyzed for PAH by capillary gas chromatography and high-performance liquid chromatography, respectively. Since benzo(a)pyrene is activated to 7 beta,8 alpha-dihydroxy-(9 alpha,10 alpha)-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDE) and binds to DNA, we have used ultrasensitive enzymatic radioimmunoassay and synchronous fluorescence spectrophotometry to measure BPDE-DNA adducts in lymphocyte DNA. The results show that workers were exposed to high concentrations of atmospheric PAH. However, the mean PAH exposure levels are reduced 60% when the workers wore masks during work. When compared to exposure levels, the urinary excretion of PAH was relatively low. Approximately one-third of the workers had detectable putative BPDE-DNA adducts in lymphocytes by ultrasensitive enzymatic radioimmunoassay, and 10% of the samples had emission peaks at 379 nm by synchronous fluorescence spectrophotometry. The four most positive samples were the same in both of the assays. Antibodies to an epitope(s) on BPDE-DNA were found in the sera of approximately one-third of the workers. Detection of DNA adducts and antibodies to these adducts are internal indicators of exposure to benzo(a)pyrene.
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PMID:Determination of polycyclic aromatic hydrocarbons in the urine, benzo(a)pyrene diol epoxide-DNA adducts in lymphocyte DNA, and antibodies to the adducts in sera from coke oven workers exposed to measured amounts of polycyclic aromatic hydrocarbons in the work atmosphere. 373 Oct 85

A canine model of squamous cell lung cancer has been developed through studies with 110 dogs exposed by 11 focal endobronchial regimens to chemical carcinogens: benzo(a)pyrene, nitrosomethylurea, methylcholanthrene, and dimethylbenzanthracene. A combination of nitrosomethylurea and benzo(a)pyrene caused the first invasive cancer after 5.5 years. Toxic side-effects resulted from either nitrosomethylurea or high-dose dimethylbenzanthracene given by bronchial submucosal injection and from adjuvant immunosuppression with azathioprine and corticosteroids. Four regimens in 58 dogs caused 31 cancers, including five T1-2 N0 M0 cancers, 17 metastasizing carcinomas, and nine carcinomas of lesser stages. The following regimens caused cancers: sequential benzo(a)pyrene, nitrosomethylurea, and yttrium 91; benzo(a)pyrene and topical nitrosomethylurea; low-dose dimethylbenzanthracene; high-dose methylcholanthrene. The most suitable regimen to date has been 30 mg of methylcholanthrene given by submucosal injection every 2 to 3 weeks; this produced cancers at preselected sites within 2 years of first exposure in eight of 10 dogs. The neoplastic continuum has followed a predictable, reproducible sequence that regularly began with epithelial hyperplasia. Squamous metaplasia occurred in 6 to 18 weeks; it was followed by progressive squamous atypia. The interval until invasive cancer developed varied with the regimen employed; it was about 20 months with methylcholanthrene. Serial cytologic specimens, studied by image analysis, revealed progressive increase in mean total cellular deoxyribonucleic acid content from diploid in normal cells to greater than tetraploid in cancer cells (p less than 0.01). We have recently been successful with serial passage of four canine lung cancers from four to twelve transplant generations in nude mice. There is now a predictable large animal model of squamous cell lung carcinoma at preselected site(s) that closely resembles human lung cancer. The preneoplastic period is short enough to be fiscally defensible, but long enough to permit study of the biologic changes during endobronchial carcinogenesis.
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PMID:Endobronchial carcinogenesis in dogs. 377 44

The inducibility of sister chromatid exchanges (SCEs) by benzo(a)pyrene (BP) was studied in cultured peripheral blood lymphocytes of 15 untreated lung cancer patients and 25 healthy persons including 11 high- and 14 low-cancer-risk individuals tentatively classified by the familial history of lung cancer and other neoplasms. The baseline SCE frequency in cultured lymphocytes was significantly high in lung cancer patients, as compared with all healthy persons or low-cancer-risk individuals. Following exposure to BP, the lymphocytes of lung-cancer patients and high-cancer-risk individuals exhibited significantly greater SCE yields than those of persons at low risk, although no significant difference was observed in the lymphocyte SCE yields when the levels of lung cancer patients were compared with those of all healthy persons. A comparison of the net SCE increase (delta SCE) in BP-exposed lymphocytes among the study groups, however, revealed a significant difference in delta SCE values only between high- and low-cancer-risk individuals. The present findings on both the observed SCE yields and delta SCE values suggest that lymphocytes of high-risk individuals may be more susceptible to BP-induced DNA damage than those of persons at low risk, and that such a chromosomal hypersensitivity to genotoxins may be associated with a high risk of neoplasms.
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PMID:Sister chromatid exchange induction by benzo(a)pryene in cultured peripheral blood lymphocytes of lung cancer patients and healthy individuals with or without familial history of neoplasms. 381 23


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