摘要:

Enhancement of lung antioxidant capacity has been proposed in the therapy of acute lung injuries involving local accumulation of reactive oxygen species (ROS). We have studied in the female Sprague-Dawley rat the effect of intratracheal administration of catalase (CAT) on the acute lung response induced by different ROS generating systems. The lung response was assessed at several time intervals (60-360 min) by monitoring in bronchoalveolar fluid (BALF) the activity of lactate dehydrogenase and the levels of total protein, albumin, and glucose. While CAT (50,000 IU/rat) significantly reduced the biochemical changes induced by hydrogen peroxide produced by a glucose/glucose oxidase system, it markedly exacerbated the lesions induced by phorbol myristate acetate (PMA). Several observations indicate that a particular chemical species formed during the catalase inactivation process is responsible for this effect. Parallel to the development of the lung damage, we noted a rapid reduction of CAT activity (80%) in the BALF of animals treated with PMA and CAT. In vitro an inhibition of CAT activity was observed in the presence of a superoxide anion generating system, and this inhibition was prevented by superoxide dismutase (SOD). A dose of 10,000 IU superoxide dismutase did not prevent the development of the lung lesions induced by PMA plus CAT. Administered alone or in association with PMA, CAT inactivated by heat or 3-aminotriazole also caused severe lung damage. In conclusion, the present study indicates that exogenous catalase may not always protect against the inflammatory reaction resulting from an oxidative stress. In the presence of superoxide anions, catalase may aggravate the lesions, and this possibility should be kept in mind when considering an antioxidant therapy.

ISSN:0098-4108    

DOI:10.1080/009841096161500

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

Six-week-old ferrets were exposed head-only to clean air or environmental tobacco smoke (ETS) at an average particulate concentration of 38 +/- 13 mg/m3 for 2 h/d, 5 d/wk for up to 15 wk. Twenty-four hours after the last exposure, the ferrets were sacrificed and the metabolism of benzo[a]pyrene and (-)-7 R-trans-benzo[a]pyrene-7,8-dihydrodiol was studied in lung homogenates. The results show that after ETS exposure total metabolism of benzo[a]pyrene, measured by the accumulation of hexane nonextractable radioactivity, was increased by 35% in the males and 66% in the females (p<.05), respectively, of that observed with air-exposed controls. With (-)-7 R-trans-benzo[a]pyrene-7,8-dihydrodiol as substrate, the formation of both benzo[a]pyrene-r-7, t-8,9, c-10-tetrahydrotetraol and (+)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-derived tetraols by lung homogenates of ETS exposed male and female ferrets was significantly increased compared to the air-exposed controls (p<.01). DNA-bound radioactivity was significantly increased in both the males (p<.01) and females (p<.05) compared to the air-exposed ferrets.

ISSN:0098-4108    

DOI:10.1080/009841096161519

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

Exposure to radon and its progeny induces significant damage to the cells of the respiratory tract and causes lung cancer. Whether a similar exposure to radon would alter the functions of the immune system has not been previously investigated. In the current study, we investigated the effect of exposure of C57BL/6 mice to 1000 or 2500 working-level months (WLM) of radon and its progeny by inhalation, on the number and functions of T lymphocytes in lymphoid organs. The control mice received uranium ore dust carrier aerosol by inhalation. Exposure to radon induced marked decrease in the total cellularity of most lymphoid organs such as thymus, peripheral lymph nodes (PLN), and lung-associated lymph nodes (LALN), when compared to the controls. The percentage of T cells increased, while that of non-T cells decreased, in all peripheral lymphoid organs at both the doses of radon. In the thymus, particularly at 2500 WLM of radon exposure, there was a marked decrease in CD4+CD8+ T cells and an increase in the immature CD4-CD8-T cells. Such alterations in both the numbers and percentages of lymphocytes and macrophages in radon-exposed mice may have resulted from the cell killing by the alpha particles as the immune cells were migrating through the lungs, or it may have been caused by altered migration of cells, inasmuch as expression of CD44, a molecule involved in migration and homing of immune cells, was significantly altered on cells found in different lymphoid organs. In the LALN, where one would predict the largest number of damaged cells to be present, there was a significant decrease in the T-cell responsiveness to mitogens while the B-cell response was not affected. Such alterations may have resulted from the direct effect of alpha-particle exposure on the migrating lymphocytes, altered percentage of lymphocytes as seen in secondary lymphoid organs, or altered expression of adhesion molecules involved in cell activation such as CD44 and CD3. Interestingly, radon exposure caused an increase in the T-and B-cell responsiveness to mitogens in the spleen and PLN. Since there is little evidence of direct radiation dose from radon in lymphoid organs, our studies demonstrating imm unological alterations suggest an indirect effect of radon exposure that may have significant repercussions on the development of hypersensitivity and increased susceptibility to infections and cancer in the lung.

ISSN:0098-4108    

DOI:10.1080/009841096161528

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

The maternal-fetal exchange of the potent tobacco-related human carcinogen 4-aminobiphenyl was studied in women smokers during pregnancy. The number of cigarettes smoked per day by each of the women in the study was assessed via questionnaire and by measurement by immunoassay of serum and urine cotinine in maternal and fetal blood samples. Maternal and fetal blood samples were classified as coming from nonsmokers (n=74), individuals smoking less than 1 pack of cigarettes per day (n=16), individuals smoking 1 pack of cigarettes per day (n=19), individuals sm oking 1-2 packs of cigarettes per day (n=19), and individuals smoking greater than 2 packs of cigarettes per day (n= 20). Both maternal and fetal blood samples were obtained at the time of delivery. 4- Aminobiphenyl was extracted from both maternal and fetal blood samples using organic extractions and the released amine was qualitatively and quantitatively characterized by analysis of the samples by gas chromatographic and mass spectrometric analysis. Background levels of 4-aminobiphenyl-hemoglobin adducts were detected in maternal nonsmokers (18.3 +/- 12.7 pg 4-aminobiphenyl/g hemoglobin, mean +/- SD) and in fetal samples (8.88 +/- 5.8 pg/g hemoglobin). Increasing levels of 4-aminobiphenyl-hemoglobin adducts were found as the smoking status of the women increased, ranging from 144 +/- 22.2 (<1 pack/d) to 633 +/- 87.9 (>2 packs/d). A corresponding increase in the presence of fetal 4- aminobiphenyl-hemoglobin adducts was also detected (74.3 +/- 17.8, <1 pack/d, to 319 +/50.5, >2 packs/d). This study confirms that the potent tobacco-related carcinogen 4-aminobiphenyl crosses the human placenta and binds to fetal hemoglobin in significantly higher concentrations in smokers when compared to nonsmokers.

ISSN:0098-4108    

DOI:10.1080/009841096161537

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

Trimethyltin (TMT) produces unique pathological and behavioral changes after a single dose. In this study, TMT was used to examine the ability of a neurobehavioral screening battery (functional observational battery and motor activity) to characterize these behavioral changes in rats. The behavioral profile of TMT was obtained using these tests in male Long-Evans (LE) and Fischer 344 (F344) rats, to assess the influence of rat strain, and in LE males and females, to evaluate gender-related differences. All rats were tested before dosing and again at 1, 7, 21, and 42d after a single dose of either 0, 4, 6, or 8 mg/kg TMT-hydroxide (intravenously). In general, the characteristic syndrome of tremor, increased reactivity, and hyperactivity was observed; however, the magnitude and time course of these effects were much greater in F344 rats. Significant strain-but not gender-related differences were obtained when comparing TMT effects on different domains of neurological function. Comparisons of predosing data between male LE and F344 rats, as well as between male and female LE rats, revealed significant differences in baseline values for about half of the measures of the test battery. These preexisting differences, however, could not account for the observed dissimilarities in treatment effects. Quantitative and qualitative differences were evident to a greater extent when comparing LEs and F344s than between males and females. Therefore, conclusions based on these types of neurobehavioral screening data would be influenced considerably more by the differences between rat strains.

ISSN:0098-4108    

DOI:10.1080/009841096161546

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

Nitrated polycyclic aromatic hydrocarbons (nitro-PAHs) are direct-acting mutagens and carcinogens that are considered a risk to human health. We investigated the metabolism of 2- nitrofluorene by the fungus Cunninghamella elegans ATCC 36112. At 144 h of incubation, C. elegans had metabolized about 81% of the [9-14C]-2-nitrofluorene, resulting in 6 metabolites. The major metabolites were separated by reversed-phase high-performance liquid chromatography and identified by 1H NMR, ultraviolet (UV)-visible, and mass spectral analyses as 2-nitro-9-fluorenol, 2-nitro-9-fluorenone, 6-hydroxy-2-nitrofluorene, and sulfate conjugates of 7-hydroxy-2-nitro-9-fluorenone and 7-hydroxy-2-nitrofluorene. 2-Nitro-9-fluorenol accounted for about 62% of the total metabolism. For comparison with the microbial system, experiments with liver microsomes of rats pretreated with 3-methylcholanthrene were conducted. Microsom al incubations indicated formation of phenolic and ring-hydroxylated products of 2-nitrofluorene. 2-Nitrofluorene and hydroxylated metabolites have been previously implicated as direct-acting mutagens in bacterial assays and have shown sister chromatid exchanges in vivo in bone marrow cells and in vitro in ovary cells and unscheduled DNA synthesis in mammalian studies. Previous studies with other PAHs using C. elegans have shown that the phenols and glucoside and sulfate conjugates of phenols are generally less mutagenic than the parent. The results from the metabolism of 2-nitrofluorene by C. elegans suggest the detoxification potential of this fungus.

ISSN:0098-4108    

DOI:10.1080/009841096161555

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

Irreversible liver cirrhosis was induced in rats by supplementing their diet with 0.02% azathioprine and intubating them twice a week with carbon tetrachloride in corn oil. Over a period of 3 mo, intoxicated rats showed an atypical acute-phase reaction (APR). The relative concentrations of haptoglobin,-lipoprotein,-1-antitrypsin, an unknown peak "X," and transferrin increased exponentially following a mild initial drop, while album in, C 3c + C 3, -1-acid glycoprotein,-1-lipoprotein, and macroglobulin declined continually during the experiment. The accumulated peritoneal fluid was found to contain a similar spectrum of APR proteins. On the other hand, histological examination revealed gradual liver damage manifested as a gradual increase in the areas of collagen separating liver cells, and at the end of the experiment, severe liver damage was evident with isolated hepatocytes in a matrix of collagen. The available data point to the disparity that exists between the physical status of hepatocytes and their biochemical function, which suggests that the remaining metabolically fatigued hepatocytes of the cirrhotic liver continue to biosynthesize and release elevated concentrations of some secretable APR proteins and less of others. Changes in the spectrum of APR plasma components during the progression of inflammatory or physical lesion remain a valid biochemical measure of the pathological function of the acutely intoxicated liver. Partial hepatectomy (PH) of cirrhotic liver displayed a mute APR and no regenerative activity of the remnant hepatic tissue, most likely due to the substantial depletion of hepatic DNA and possible chemical damage to DNA of the remaining viable hepatocytes. A possible cause for the depressed APR to the surgical insult of PH is that the initial azathioprine CCl4 intoxication had maximally affected APR gene expression and a second injury would then elicit minimal further changes in m RNA levels. Thus, in a compounded pathological condition, the initial inflammatory stimulus on various pre-rRNAs, rRNAs, and mRNAs is rate-limiting to the hepatic biosynthesis and secretion of APR proteins and may not respond linearly, if at all, to a second stimulus.

ISSN:0098-4108    

DOI:10.1080/009841096161564

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor