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

Aryl hydrocarbon hydroxylase activity in lymphoblasts from normal Finnish adults and from patients with pulmonary carcinomas and other types of malignancy has been studied by a modification of previously used techniques. High absolute induced aryl hydrocarbon hydroxylase activity was found in 39% of patients with untreated lung cancer but only in 15% of normal people. No increased frequency was found in the control group comprising other malignancies. The diagnosis of pulmonary carcinoma was made at a lower mean age (4.9 years younger) in the individuals with high aryl hydrocarbon hydroxylase activity than in those with low activity. High absolute aryl hydrocarbon hydroxylase activity was dominantly inherited in normal individuals, and the frequency of athe Ahb gene in the Finnish population was 8%.
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PMID:Induction of aryl hydrocarbon hydroxylase activity and pulmonary carcinoma. 43 13

A very large variation (44-fold) was observed in the ability of short-term organ cultures of peripheral lung tissue from lung-cancer patients to metabolize the environmental carcinogen benzo(alpha)pyrene to organic solvent-soluble metabolites. The amounts of benzo(alpha)pyrene (2 microM) metabolized ranged from little (1%) to almost total (96.2%) metabolism within 24 h of culture. Previous work by Kellerman et al. (1973) has suggested a relationship between susceptibility to lung cancer and the indicibility of aryl hydrocarbon hydroxylase activity in cultured human lymphocytes. The metabolic fate of carcinogenic polycyclic aromatic hydrocarbons in the respiratory tract in vivo is undoubtedly more closely mimicked by short-term organ culture of human lung than by cultured lymphocytes. Thus the very wide interindividual variation observed in pulmonary metabolism of benzo(alpha)pyrene in this study and the large variations in covalent binding to human bronchial DNA observed by Harris et al. (1976) strongly suggest that there may be little basis for screening humans for variations in lymphocyte aryl hydrocarbon hydroxylase activity as a means of assessing their susceptibility to lung cancer.
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PMID:Large interindividual variations in metabolism of benzo(alpha)pyrene by peripheral lung tissue from lung cancer patients. 48 61

Exposure to whole cigarette smoke from reference cigarettes results in the prompt (peak activity is 6 hrs), but fairly weak (similar to 2 fold), induction of murine pulmonary microsomal monooxygenase activity. This activity can be detected by using as substrates either benzo(a)pyrene or ethoxyresorufin, and can be inhibited by treatment with cycloheximide or actinomycin D. Unlike the induction of pulmonary monooxygenases following intratracheal administration of 3-methylcholanthrene, these cigarette smoke-induced increases were not unequivocally linked to the Ah locus. Whole smoke condensate and fractions derived from these condensates can; a) induce pulmonary monooxygenase activity, b) inhibit benzo(a)pyrene metabolism in vitro, c) be metabolized to forms mutagenic to Salmonella typhimurium tester strains TA153, or TA98, d) transform C3H 10T1/2 cells in vitro, and e) enhance the carcinogenicity of benzo(a)pyrene in murine pulmonary tissue. A potentially important observation is that whereas hepatic tissue is capable of activating whole cigarette smoke condensate to mutagenic forms in vitro, murine pulmonary tissue does not seem capable of such activation. Although these pulmonary-derived tissue homogenates have significant AHH activity and can metabolize Aflatoxin B1, 2-aminofluorene and 7, 8-dihydro-7,8-dihydroxybenzo(a)pyrene to mutagenic forms, these homogenates fail to activate both cigarette smoke condensate and the pro-mutagen, 6-aminochrysene. These results are discussed with reference to the concept that whole cigarette smoke may be both a potential "initiator" and "promotor" of lung cancer in mice, and that this latter property may be the most important in determining cancer risk.
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PMID:Biological activity of tobacco smoke and tobacco smoke-related chemicals. 51 Feb 43

We measured aryl hydrocarbon hydroxylase (AHH) in cultured human lymphocytes. A striking seasonal variation in AHH activity was observed with induced AHH activity levels from January through May measuring approximately 20% of the values during the remainder of the year. AHH inducibility was determined by comparing lymphocytes from the same person cultured with and without the inducer 3-methylcholanthrene. If measurements are limited to the summer and fall seasons when AHH activity is high, AHH inducibility is reproducible for most persons with repeat determinations on the same person averaging 11% from the mean. The values of AHH inducibility in 53 persons ranged from 0.9 to 5.0, but the distribution of values did not fall into three distinct, nonoverlapping classes as reported by others. We were not able to determine the distribution of AHH inducibility in lung cancer patients since lymphocytes from less than half of the patients tested could be successfully cultured.
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PMID:Distribution of aryl hydrocarbon hydroxylase inducibility in cultured human lymphocytes. 87 Jan 87

To test whether the genetically determined trait, aryl hydrocarbon hydroxylase inducibility, affects susceptibility to lung cancer, we measured this trait in cultured lymphocytes from a normal population, patients with lung cancer and progeny of such patients. We found very low aryl hydrocarbon hydroxylase activity (19 per cent of normal) in about half the patients with lung cancer. Only part of this activity can be accounted for by reduced cell growth and by reduced protein synthesis. In an indirect assessment of inducibility, both 57 progeny and 27 matched controls had a mean inducibility of 2.95 and a similar distribution into low, intermediate and high groups (chi-square = 0.3 P = 0.9). No differences in basal or induced activity were observed. Thus, if patients with lung cancer possess altered aryl hydrocarbon hydroxylase inducibility or activity these characteristics are not transmitted to their progeny.
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PMID:Questionable relation of aryl hydrocarbon hydroxylase to lung-cancer risk. 87 25

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

Genetic modulation of environmental exposures associated with common malignancies is an attractive mechanism to explain differential susceptibility to tobacco or occupation-related carcinogens in the population. The paper reviews the evidence for an association between three genetically based metabolic polymorphisms (N-acetyltransferase, Debrisoquine, hydroxylase, aryl hydrocarbon hydroxylase), which have been implicated in the modulation of lung or bladder cancer risks. Fair to good support emerged for both an association of the acetylation phenotype with occupationally related bladder cancer and for an association of the debrisoquine metabolic phenotype with lung cancer, although in neither case was the evidence completely convincing. Epidemiologic evidence for an association between aryl hydrocarbon hydroxylase and lung cancer is presently problematic because of the difficulties in the assay and subsequent confounding factors.
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PMID:[Metabolic polymorphisms and the cancer risk: the evaluation of epidemiological studies]. 129 37

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

The main polycyclic aromatic hydrocarbon-inducible cytochrome P450 was studied in lung tissue from 57 lung cancer patients by immunohistochemistry, using a monoclonal antibody (1-7-1) that recognizes P450IA1 and P450IA2 isozymes. The intensity of immunostaining was compared with the pulmonary activity of a P450IA1-dependent enzyme, aryl hydrocarbon hydroxylase (AHH), and with P450IA2-related metabolic activity estimated from the ratio of caffeine metabolites in urine. Immunostaining was not observed in peripheral lung tissue of nonsmokers or ex-smokers but was seen in the bronchiolar and alveolar epithelium of all patients who were smokers and had a peripheral carcinoma (16/16) and of 60% (10/17) of those who had a bronchial carcinoma. AHH activity was positively related to the intensity of immunostaining, and an almost 2-fold increase due to smoking was detected in the ratios of caffeine metabolites. These results demonstrate that tobacco smoke induces P450IA1 in the lung and probably P450IA2 in the liver, and suggest a role for certain metabolic phenotypes of P450IA1 in peripheral pulmonary carcinoma.
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PMID:Immunohistochemical detection of pulmonary cytochrome P450IA and metabolic activities associated with P450IA1 and P450IA2 isozymes in lung cancer patients. 133 24

An improved high-performance liquid chromatography/fluorometric assay has been established to quantitate the benzo(a)pyrene (BP) tetrols released after acid hydrolysis of lung DNA from lung cancer patients, so that the formation of benzo(a)pyrene diol-epoxide-DNA adducts can be measured. The r-7,c-10,t-8,t-9-tetrahydroxy-7,8,9,10-tetrahydro-BP isolated by high-performance liquid chromatography was determined by chromatography in two different solvent systems and fluorescence spectroscopy. This assay has a detection limit of 2 pg of r-7,c-10,t-8,t-9-tetrahydroxy- 7,8,9,10-tetrahydro-BP, requires 100-500 micrograms of DNA, and can measure 1 adduct/10(8) unmodified nucleotides. As this assay does not use immunoaffinity chromatography or solvent extraction, it allows a > 90% recovery of benzo(a)pyrene diol-epoxide-DNA adducts. This procedure has been tested on 13 DNA samples prepared from nontumorous lung parenchyma taken from lung cancer patients at surgery and revealed the presence of DNA adducts of the anti-benzo(a)pyrene diol-epoxide in 9 of 11 samples from smokers and in 2 of 2 ex-smokers. In only two samples from smokers the formation of adducts derived from syn-benzo(a)pyrene diol-epoxide was detected. A 15-fold variation in DNA adduct level was found in 11 of 13 DNA samples, with a range of 0.6-9.9 adducts of benzo(a)pyrene diol-epoxide/10(8) nucleotides. In samples containing both anti- and syn-benzo(a)pyrene diolepoxide-DNA adducts, the anti/syn adduct ratio is 2:1. A highly significant correlation was found between pulmonary microsomal aryl hydrocarbon hydroxylase activity and the level of benzo(a)pyrene diolepoxide-DNA adduct (r = 0.91; P < 0.001; n = 13). A crude linear correlation between the amounts of these adducts and those of bulky DNA adducts determined by 32P-postlabeling assay was observed in the same samples (r = 0.78; P < 0.02; n = 13). Thus this highly sensitive and specific procedure is suitable for measuring benzo(a)pyrene diolepoxide-DNA adducts in human tissues from environmentally exposed subjects and could be adapted to measure polycyclic aromatic hydrocarbons other than BP.
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PMID:An improved fluorometric assay for dosimetry of benzo(a)pyrene diol-epoxide-DNA adducts in smokers' lung: comparisons with total bulky adducts and aryl hydrocarbon hydroxylase activity. 142 69


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