摘要:

The relationship between immunotoxicity of ammonium metavanadate (NH4VO3) and levels of tumor necrosis factor-alpha(TNF-alpha) and interleukin-1 (IL-1) was studied with a NH4VO3-treated murine macrophage-like cell line, J774 and resident peritoneal macrophages (PEM) obtained from treated mice. Lipopolysaccharide (LPS)-induced elevation of extracellular TNF-alpha in PEM and J774 cells was not markedly affected by prior treatment with vanadate. However, PEM from treated mice at 10 mg V/ kg (10V) had a significantly lower level of LPS-induced intracellular TNF-alpha. NH VO-treated J774 cells at 3.6 (V1) and 437.2 mug V/107 cells (V2) had significantly higher levels of intracellular TNF-alpha than the PO4 and V3 (10.8 mug V/107 cells) groups. Although the four PEM groups showed no marked difference in extracellular IL-1 levels, PEM from treated mice at 2.5V and 10V had significantly lower levels of intracellular IL-1 than those from control groups. J774 cells from PO4 and NH4Cl groups showed significant increases in intracellular IL-1 following treatment with LPS. However, J774 cells with prior treatment with vanadate revealed significant reduction in levels of LPS-induced intracellular IL-1 when compared to control groups. Therefore, the previously reported reduced resistance of vanadate-treated mice to Listeria monocytogenes could be attributed to an inhibitory effect on the production of IL1 in macrophages.

ISSN:0098-4108    

DOI:10.1080/009841096161159

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

Gap junction intercellular communication (IC) is thought to be important in chemical carcinogenesis as abnormalities in IC have been found in cancer cells. Perchloroethylene (PERC) is metabolized in rodent liver to dichloroacetic acid (DCA) and trichloroacetic acid (TCA), which are rodent liver carcinogens. Chloral hydrate (CH) and trichloroethanol (TCEth) are kidney metabolites. We used Lucifer yellow scrape-load dye transfer as a measure of IC to look at the effect of PERC, DCA, TCA, CH, and TCEth on Clone 9 cell cultures (normal rat liver cells). Four independent experiments were performed for each chemical using exposure times of 1, 4, 6, 24, 48, and 168 h. Concentrations for each chemical varied and were based on preliminary data on effect and cytotoxicity. To compare the relative effectiveness of each chemical to cause biological change, we identified the lowest concentration and shortest time to significantly reduce dye transfer. DCA caused a significant change at 10 m M at 6 h; TCA, 1 m M at 1 h; CH and TCEth, 1 m M at 24 h; and PERC, 0.01 m M at 48 h. Over a 24-h treatment period, the relative efficiencies, as defined by the concentration needed to produce 50% reduction in IC, were PERC (0.3 mM) >> TCA (3.8 mM) > TCEth (6.6 mM)=CH(7.0 m M) >> DCA (41 mM). Timecourse data indicated that PERC, DCA, and TCA produced reduction in IC in a similar fashion, but 5 mMCH or TCEth exhibited variances from these results and may indicate specific cell responses to these chemicals. The mechanism(s) responsible for inhibition of IC by these structurally related chemicals needs to be established.

ISSN:0098-4108    

DOI:10.1080/009841096161168

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

Benzene is a known carcinogen and hematopoietic toxin in humans and experimental animals. The effect of acute, high-dose exposure to benzene on hepatic bioactivation and detoxication enzymes has been defined, while little is known about the effect of repeated, low-dose benzene exposure on these enzymes. Our objective was to determine whether repeated, oral benzene exposure alters enzymes involved in benzene metabolism. Specifically, we were concerned with cytochrome P-450-2E1, a bioactivation enzyme, and glutathione transferase and aldehyde dehydrogenase, two detoxifying enzymes. Female CD-1 mice were treated by gavage for 3 wk with benzene doses of 5 mg/kg (0.064 mmol/kg) or 50 mg/kg (0.646 mmol/kg) in corn oil. These doses of benzene produced 0.048 and 0.236 mumol muconic acid/d, respectively. We found that repeated exposure to 50 mg benzene/kg/d decreased P-450-2E1 activity by 34% and induced glutathione transferase activity by 30% without affecting aldehyde dehydrogenase activity. These changes in enzyme activities may serve a protective role against repeated exposure to benzene.

ISSN:0098-4108    

DOI:10.1080/009841096161177

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

The concentration of the urinary benzene metabolite trans,trans-muconic acid was measured after exposure to benzene contained in environmental tobacco smoke (ETS). Volunteers were exposed to environmental tobacco smoke at different exposure levels and for different exposure durations. Urine samples were collected preexposure and postexposure for 24 h on exposure days. To determine background levels, urine samples were also collected on three individual days when no exposure to ETS occurred. Urinary muconic acid was elevated following benzene exposure in ETS compared to an individual's background level and can be a useful biomarker in control, characterized studies of sub-partsper-million (sub-ppm) benzene exposures. However, the use of muconic acid as a biomarker of benzene exposure at sub-ppm levels in the general population is problematic because of variability in the time between exposure and excretion and in an individual's background excretion rate. Urinary muconic acid associated with benzene in ETS exposure was excreted within 12 h of the exposure. A higher proportion of the benzene dose following environmental exposure in the sub-ppm range was excreted as urinary muconic acid (mean of 25%, range 7.2-58%) than found in either animal or occupational studies at higher benzene doses. The higher proportion of benzene excretion as urinary muconic acid at low benzene exposure indicates that the relationship between exposure and metabolism by the ring opening pathway is nonlinear in humans, and extrapolation from high doses to environmental benzene exposure potentially underestimates health risks mediated by the ring opening metabolic pathway that produces muconic acid, as has been suggested by previous animal data.

ISSN:0098-4108    

DOI:10.1080/009841096161186

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

In this study, we evaluate the significance of increased urinary chromium concentrations as a marker of chromium exposure and potential health risk. Six human volunteers ingested trivalent chromium [Cr(III)] and hexavalent chromium [Cr(VI)] at doses that are known to be safe but are much higher than typical dietary levels. The following dosing regimen was used: d 1-7, 200 mug/d chromium picolinate (a dietary supplement); d 8-10, Cr(VI) ingestion at the U.S. Environmental Protection Agency (EPA) reference dose (RfD) of 0.005 mg/kg/d; d 11-13, no dose; d 14-16, Cr(III) ingestion at the U.S. EPA RfD of 1.0 mg/kg/d; and d 17-18, postdose. Urine voids were collected throughout the dosing periods and analyzed for chromium. Our findings are as follows: (1) ingestion of 200mug/d of chromium picolinate yielded significantly elevated urine concentrations such that each participant routinely exceeded background, (2) ingestion of the Cr(VI) RfD (0.005 mg/kg/d) yielded individual mean urinary chromium levels (1.2-23 mug/L) and a pooled mean urinary chromium level (2.4 mug/L) that significantly exceeded background, and (3) ingestion of the Cr(III) RfD yielded no significant increase in urinary chromium concentrations, indicating that little, if any, absorption occurred. Our work identified three critical issues that need to be accounted for in any future studies that will use urinary chromium as a marker of exposure. First, a minimum urinary chromium concentration of approximately 2mug/L should be used as a screening level to critically identify individuals who may have experienced elevated exposures to chromium. Second, if Cr(III) levels in soils are known to be less than 80,000 ppm and the Cr(III) is insoluble, urinary chromium concentrations are not an appropriate marker of exposure. Third, newer forms of chromium supplements that contain organic forms of Cr(III) must be considered potential confounders and their contribution to residential chromium uptake must be carefully evaluated.

ISSN:0098-4108    

DOI:10.1080/009841096161195

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

Because some evidence suggests that there may be an increased incidence of lung cancer in silicosis and because previous studies have shown that exposure of rats to silica alters the pulmonary cytochrome P-450 system, we studied the effects of exposing rats to silica on the lung microsomal metabolism of benzo[a]pyrene (BaP). Rats were exposed to silica by intratracheal administration, lung microsomes were obtained 2 wk later from untreated and silica-treated animals, and the amounts of microsomal tissue and metabolites formed during the in vitro microsomal metabolism of BaP were measured. When the formation of BaP metabolites in equal amounts of lung microsomal tissue from the 2 treatment groups is compared, 3-OH BaP, BaP 4,5-diol, and BaP 9,10-diol are reduced by 45-70%, but the formation of BaP 7,8-diol or the BaP-quinones is not significantly altered following exposure to silica. In fact, the ratio of the BaP diols and BaP quinones, potentially toxic metabolites, to the relatively nontoxic 3-OH BaP produced by equal amounts of lung microsomal tissue is increased more than threefold following exposure of rats to silica. Since exposure of rats to silica leads to increased levels of lung microsomal protein, the amounts of BaP metabolites that could be produced by all microsomal tissue in the lungs were calculated. In silicatreated animals, the calculated total lung production of 3-OH BaP, BaP 4,5-diol, and BaP9, 10-diol tends to be increased by 1.2- to 2.0-fold, but BaP 7,8-diol and the BaP quinones are increased by 3.5-fold. These results demonstrate that exposure of rats to silica may alter the capacity of the lungs to metabolize benzo[a]pyrene, and the greatest effect seems to be enhanced accumulation of BaP 7,8-diol and the BaP quinones.

ISSN:0098-4108    

DOI:10.1080/009841096161203

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor

摘要:

The neurotoxic action of a synthetic pyrethroid, a deltamethrin formulation (Decis), was studied in adult rats. Adult male albino rats received deltamethrin in formulation at a dose of 7.0 mg/kg body weight/d in corn oil orally for 15 d. Deltamethrin-exposed rats exhibited a decrease in body weight from d 9 onward, which was significantly lowered at d 15 of exposure. Administration of deltamethrin markedly increased the wet weight of the hippocampus and pons medulla region without much affecting the weight of frontal cortex, corpus striatum, hypothalamus, and cerebellum. A significant increase in the activity of monoamine oxidase was observed in frontal cortex, hippocampus, and cerebellum, and acetylcholinesterase activity was markedly increased in frontal cortex, corpus striatum, hippocampus, cerebellum, and pons medulla. The activity of Na+,K+-ATPase showed marked decrease in frontal cortex, hippocampus, and cerebellum following deltamethrin exposure. The polyamine concentration in brain regions was significantly affected, and all three polyamines showed marked alterations in the cerebellum. Deltamethrin significantly increased the spontaneous locomotor activity and aggressive behavior. Maze learning was markedly decreased. Morphological changes in Purkinje neurons in the cerebellum were observed in deltamethrin-exposed rats. Results suggest significant neurochemical and neuromorphological changes, which may culminate in perturbed synaptic function following deltamethrin exposure in rats.

ISSN:0098-4108    

DOI:10.1080/009841096161212

出版商:Informa UK Ltd    

年代:1996

数据来源: Taylor