摘要:

Glutathione S‐transferase isozyme class mu from human leukocytes has been shown to be dominantly inherited and can be determined by activity measurement directed toward the substrate trans‐stilbene oxide. The activity distribution of leukocyte glutathione S‐transferase class mu was determined from control healthy nonsmokers, smokers, and smoking‐related cancer patients. In a control healthy nonsmoker population, 54% (n = 50) of the subjects showed high levels of glutathione S‐transferase class mu activity. In patients with cancers known to be related to smoking, 46% (n = 50) showed higher levels of glutathione S‐transferase class mu. Noncancer smokers matched for age and smoking history with cancer patients showed an increased likelihood of having glutathione S‐transferase (GST) class mu activity (76%). These results suggest that GST mu may be a cancer susceptibility marker in the case of smokers. In rats, benzo[a]pyrene (1 mg/kg, ip) administration daily for 3 d produced a significant increase in liver glutathione S‐transferase class mu. Although these induction studies in experimental animals may not be relevant to humans, there is a possibility that, as in rats, this enzyme may be inducible in humans by polycyclic aromatic hydrocarbons.

ISSN:0098-4108    

DOI:10.1080/15287399509532013

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Eicosanoids and cytokines produced by alveolar macrophages (AM) are key mediators of pulmonary inflammation and fibrosis. In order to determine if eicosanoid production and cytokine production are altered in AM obtained from coal miners, we compared production of prostaglandin E2(PGE2), thromboxane A2(TXA2), leukotriene B4(LTB4), interleukin‐1 beta (IL‐1β), and tumor necrosis factor alpha (TNFα) by cultured AM from normal human subjects and coal miners. The recovery of AM from miners’ lungs by bronchoalveolar lavage was significantly greater than that from control subjects. Mean eicosanoid and cytokine production by AM from active miners was also increased compared to AM from control subjects, but this increase was not statistically significant. AM from control subjects produced significantly more TXA2and TNFα when exposed to lipopolysaccharide than did AM from miners. The cyclooxygenase inhibitor suprofen reduced PGE2and TXA2production and TNFα release but had no effect on LTB4production or IL‐1β release by miners’ AM. The lipoxygenase inhibitor nordihydroguaiaretic acid attenuated TNFα release, as well as that of LTB4, but had no effect on IL‐1β release. Inhibition of thromboxane synthase by UK 38,485 also reduced TNFα release by active miners’ AM but had no effect on PGE2, LTB4production, or IL‐1β release. The results of these studies suggest that occupational inhalation of coal dust may increase total lung eicosanoid and cytokine levels and reduce the reactivity of AM to bacterial endotoxin. Furthermore, coal dust‐induced changes in both eicosanoid and cytokine release may be subject to pharmacological modulation.

ISSN:0098-4108    

DOI:10.1080/15287399509532014

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

The oxygen dependence of ethane formation was investigated in rat lung and liver homogenates, incubated in sealed flasks, in which the peroxidation was stimulated by the addition of ferrous ions. For both tissues, the production of ethane was maximal under a 20% oxygenated gas phase, while hyperoxic conditions led to a decreased ethane in the gas phase. The formation of thiobarbituric acid‐reactive substances (TBA‐RS), another marker of the lipid peroxidation process, in the homogenates of lung and liver was strongly stimulated at 100% compared to 20% oxygen. Experiments were also carried out on iron‐stimulated peroxidation of pure docosahexaenoic acid preparations, which under air led to a large production of ethane. As for tissue homogenates, the TBA‐RS content was increased in the presence of 100% oxygen. Those conditions, however, did not induce an increase in ethane production but led to the formation of ethanol. Therefore, the quenching of ethyl radical by molecular oxygen seems to be a very attractive hypothesis to explain the lack of increased ethane production in favor of ethanol when iron‐induced lipid peroxidation was stimulated by oxygen.

ISSN:0098-4108    

DOI:10.1080/15287399509532015

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Chronic exposure to dimethylnitrosamine produces hepatic tumors through recurrent DNA alkylation, whereas acute exposure can cause liver necrosis through mechanisms that remain largely unknown. Our laboratory recently demonstrated that DNA fragmentation occurs early on and may be a causal event in dimethylnitrosamine‐induced necrosis in liver. A challenge to interpreting these results is that up to 30% of liver cells are non‐parenchymal and could account for the observed DNA fragmentation. In the present study, we have examined whether dimethylnitrosamine induces early genomic DNA fragmentation in cultured mouse hepatocytes. Hepatic parenchymal cells isolated from male ICR mice were cultured in Williams E medium. DNA damage was assessed quantitatively as a fragmented fraction that was not sedimented at 27,000 × g, and qualitatively from agarose gel electrophoresis. Cellular response to DNA damage was assessed by measuring induction of the DNA repair enzyme DNA ligase. Toxic cell death was estimated from release of lactate dehydrogenase (LDH) or adenine nucleotides from cells prelabeled with [3H]adenine. Dimethylnitrosamine produced a twofold increase in [3H]adenine release by 6 h and LDH release at 36 h. DNA fragmentation and DNA ligase activity increased by as early as 1 h. The Ca2+‐endonuclease inhibitor aurintricarboxylic acid and the Ca2+chelator ethylenediamine tetraacetic acid (EDTA) prevented DNA fragmentation through 6 h and virtually abolished cytotoxicity through 30 h. DNA ligase induction was strongly associated with DNA fragmentation. Early increases in DNA fragmentation and DNA ligase were highly correlated with later toxic cell death. Such results strongly suggest that dimethylnitrosamine‐induced fragmentation of DNA in target parenchymal cells is a causal factor in the toxic death of these liver cells.

ISSN:0098-4108    

DOI:10.1080/15287399509532016

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Cytochrome P‐450 monooxygenases of golden Syrian hamsters were characterized with respect to benzo[a]pyrene metabolism. Male hamsters were treated with phenobarbital, 3‐methylcholanthrene, dexamethasone, benzoflavone, or ethanol, and the activity of aryl hydrocarbon hydroxylase and benzo[a]pyrene activation was determined by mutagenicity testing in hepatic microsomes. Aryl hydrocarbon hydroxylase activity was induced markedly by treatment with phenobarbital but not with 3‐methylcholanthrene, nor with other chemicals. The degree of benzo[a]pyrene activation on mutagenicity testing was significantly elevated by treatment with 3‐methylcholanthrene and phenobarbital but was reduced with dexamethasone. Immunoinhibition of these activities and Western blotting of hepatic microsomes using antibodies against cytochrome P‐450 isozymes suggested that the isozymes responsible for benzo[a]pyrene metabolism in Syrian hamsters belong to the CYP1A, CYP2A, and CYP3A families, a result that differs from observations in rats.

ISSN:0098-4108    

DOI:10.1080/15287399509532017

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

We studied the hematological effects of single and repeated exposure to 1,3,5‐trinitroben‐zene (TNB) in rats. Male F‐344 rats were gavaged with TNB at 35.5 and 71 mg/kg in corn oil. Blood was collected 5 h and 24 h after a single oral dose or 24 h after daily oral doses for 4 or 10 d in four different set of experiments. A dose‐dependent methemoglobinemia was present only in blood collected 5 h after a single dose. A highly significant dose‐dependent anemia with reduced red cells, hemoglobin, and hemotocrit was present in rats receiving TNB (or 4 or 10 d. A dose‐dependent decrease in serum triglycerides was present in rats receiving TNB for 10 d. There was no hemolysis when rat erythrocytes were incubated with TNB (in vitro) for 9 h. Spectral changes of hemoglobin recorded during the incubation with TNB confirm methemoglobin formation and progressive denaturation of hemoglobin‐forming hemichromes. The significance of methemoglobin and hemichrome formation is discussed, and a probable hypothesis for the hemolytic anemia is suggested.

ISSN:0098-4108    

DOI:10.1080/15287399509532018

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

The principle aim of the present study was to provide evidence for the existence of both a luminal and a basolateral mechanism involved in the renal tubular uptake of inorganic mercury. To accomplish this aim, we examined individually and collectively the effects of a “stop‐flow” technique designed to reduce glomerular filtration to negligible levels and pretreatment with the organic anion p‐aminohippurate (PAH) on the renal uptake and disposition of administered inorganic mercury. More specifically, we compared the disposition of inorganic mercury in groups of surgical control rats, rats that underwent a unilateral ureteral ligation, and rats that underwent a bilateral ureteral ligation that were pretreated with either normal saline or a 7.5 mmol/kg intravenous dose of PAH 5 min prior to receiving a nontoxic 0.5‐μmol/kg intravenous dose of mercuric chloride. The disposition of mercury was evaluated at both 1 h and 24 h after the dose of inorganic mercury had been administered. In brief, the “stop‐flow” conditions induced by either unilateral or bilateral ureteral ligation caused a significant reduction in the uptake and content of mercury in the kidneys (whose ureter was ligated) both at 1 h and 24 h after the intravenous injection of the nontoxic dose of mercuric chloride. This decreased renal uptake of mercury was due specifically to decreased uptake of mercury in the renal cortex and outer stripe of the outer medulla. Assuming that glomerular filtration was reduced to negligible levels, the amount of mercury not taken up during ureteral ligation represents the portion of mercury that is presumably taken up by a luminal mechanism. Pretreatment with PAH also caused a significant reduction in the renal uptake of mercury, specifically in the cortex and outer stripe of the outer medulla. The effects were most prominent 1 h after the injection of inorganic mercury. When either unilateral or bilateral ureteral ligation was combined with PAH pretreatment, an additive inhibitory effect occurred with respect to the renal uptake of mercury. In fact, the renal uptake of mercury was reduced by approximately 85% at 1 h after the injection of mercuric chloride. Since the luminal uptake of mercury was blocked by ureteral ligation, the effect of PAH on the renal uptake of mercury must have occurred at the basolateral membrane. Thus, the findings from the present study indicate that there are two distinct mechanisms involved in the uptake of mercury, with one mechanism located on the luminal membrane and another located on the basolateral membrane (presumably on proximal tubular epithelial cells).

ISSN:0098-4108    

DOI:10.1080/15287399509532019

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

Water, sediment, and fish were sampled from three streams that were receiving or had received effluents from oil refineries. Water and sediment samples were analyzed by gas chromatographylmass spectrometry. Each stream contained aromatic carbons including substituted benzenes and naphthalenes, which are related to oil refinery operations. Fish were identified, counted, and examined for external lesions. Lengths and weights were recorded for older bullhead catfish, and their livers were examined histologically. Differences were seen in the diversity and abundance of fish among the upstream, impacted (effluent‐receiving), and downstream stations. In one stream, differences in liver pathology were observed between reference bullhead, collected from an upstream station, and those collected at impacted stations with more than 50% of the bullheads taken from impacted stations having some sort of pathological change, including one with a liver clear‐cell focus, which is considered a preneoplastic lesion in rodents. These data suggest a correlation between contamination of water and sediments with aromatic hydrocarbons, presumably from refinery effluents, and compromised fish health.

ISSN:0098-4108    

DOI:10.1080/15287399509532020

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

摘要:

The objectives of the present study were (1) to develop an algorithm to predict tissue : blood partition coefficients (PCs) of organic chemicals from n‐octanol : water (Ko/w) PC data, and (2) to apply this algorithm to predict the rat tissue : blood PCs of some relatively hydrophilic organics, particularly ketones, alcohols, and acetate esters. The algorithm, developed by modifying a previously published one, involved predicting tissue : blood PCs of chemicals by dividing their partitioning into tissues by the sum of their partitioning into erythrocytes and plasma. The partitioning of a chemical into tissues, erythrocytes, and plasma was expressed as an additive function of its partitioning into neutral lipids, phospholipids, and water contained in them. The muscle, liver, and adipose tissue : blood PCs predicted with the present method were compared with the experimental values obtained from the literature for five ketones, eight alcohols, and eight acetate esters. The predicted muscle : blood and liver : blood PCs for the set of 21 hydrophilic organics were within a factor of 1.01 and 0.99 (on an average), respectively, of the experimental values. However, the predicted adipose tissue : blood PCs of the hydrophilic organics were greater than the experimental values by a factor of 4.13, which improved when vegetable oil : saline (Ko/s) PCs were used instead of Ko/wPCs (factor of 1.51). Overall, the use of the present algorithm should enable the prediction of tissue : blood PCs for organic chemicals for which Ko/wor Ko/sdata are available.

ISSN:0098-4108    

DOI:10.1080/15287399509532021

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399509532012

出版商:Taylor & Francis Group    

年代:1995

数据来源: Taylor