摘要:

Previous reports have demonstrated mercury accumulation and toxicity in oral tissues following exposure to mercury vapor from dental amalgam restorations. In the present study, inflammatory responses to subcutaneously administered mercury were assessed histopatho-logically and immunocytochemically in a rat model system. A panel of six well-characterized monoclonal antibodies specific for monocytes, macrophage subsets, T and B lymphocytes, and major histocompatibility complex (MHC) class II (la) determinants was used to quantitate alterations in mononuclear cell subsets in situ at time intervals from 2 d to 8 wk. The results revealed acute inflammatory cell infiltration at 2 and 3 d, followed by chronic inflammation that persisted after 8 wk. The numbers of monocytes, resident macrophage subsets, and mononuclear cells expressing la antigen were significantly different from control tissues at 1–2 wk. The numbers of resident macrophages remained significantly higher even after 8 wk. These data showed that in situ mercury accumulation can lead to altered expression of MHC class II determinants with persistent chronic inflammation and shifts in mononuclear cell subpopulations.

ISSN:0098-4108    

DOI:10.1080/00984108.1996.10662173

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor

摘要:

In order to investigate if hemoglobin might serve as a biomarker of exposure for 1,2- dichloroethane (DCE) encountered in the workplace, human hemoglobin was alkylated at physiologic pHby the episulfonium ion of S-(2-chloroethyl)glutathione (CEC). In vitro alkylation resulted in three alkylation products on the α chain and at least two alkylation products on the βl chain as determined directly by matrix-assisted laser desorption-ioniza tion mass spectrometry. To ascertain if the site of alkylation was the reactive sulfhydryl present at cysteine-93 on the β chain of hemoglobin (β-93Cys), a spectrophotometric assay using 4,4'-dithiodipyridine was used to measure the free sulfhydryl groups before and after treatment of hemoglobin with various amounts of CEC. Results indicate that the episulfonium ion did not react substantially at β-93Cys, as there was no measurable decrease in the sulfhydryl to hemoglobin ratio, even with a large excess of CEC. In contrast, iodoacetamide did react with the sulfhydryl groups and gave a dose-dependent decrease in the sulfhydryl to hemoglobin ratio as measured by this assay. CEC-treated hemoglobin was digested with Staphylococcus aureus endoproteinase Glu-C and the digest was analyzed by fast atom bombardment mass spectrometry. Only one peak in the FAB mass spectrum could correspond to a peptide modified by the episulfonium ion of CEC. These results indicate that although the episulfonium ion of CEC does alkylate human hemoglobin, β-93Cysis not the major alkylation target.

ISSN:0098-4108    

DOI:10.1080/00984108.1996.10662174

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor

摘要:

Bromodichloromethane (BDCM), a carcinogenic water disinfection by-product, has been shown to be metabolized to intermediates that covalently bind to lipids and proteins, and this binding has been associated with trihalomethane-induced renal and hepatic toxicity. In this study, the effects of glutathione (CSH) on in vivo BDCM toxicity and in vitro BDCM macromolecular binding were evaluated. The in vivo toxicity of BDCM in animals pretreated with buthionine sulfoximine (BSO, a glutathione synthesis inhibitor) and in untreated male Fischer 344 rats was investigated. In another experiment, covalent binding to protein and lipid was quantified after [14C]BDCM was incubated with hepatic microsomal and S9 fractions and renal microsomes from F344 rats, under aerobic and anaerobic conditions, with and without added CSH. After oral dosing with BDCM, the BSO-pretreated animals had greatly increased levels of serum indicators of hepatotoxicity and serum and urinary indicators of nephrotoxicity compared to those in animals dosed solely with BDCM. Histopathological examination revealed that hepatic necrosis was more severe than renal necrosis in the BSO-treated rats. When GSH was added to an aerobic incubation, protein binding was decreased in hepatic microsomal and S9 fractions by 92 and 83% respectively. GSH also decreased lipid binding by 55% in hepatic microsomal incubations carried out under anaerobic conditions. Addition of GSH decreased renal microsomal protein (aerobic) and lipid binding (anaerobic) by 20 and 43%, respectively. These data indicate that GSH is an important protective factor in the toxicity associated with BDCM.

ISSN:0098-4108    

DOI:10.1080/00984108.1996.10662175

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor

摘要:

Fusaric acid is produced by several species of Fusarium and is found in corn, corn-based foods and feeds, wheat, barley, and other cereal grains. Given parenterally to rats, the mycotoxin affects neurochemical parameters in the pineal gland associated with growth and maturation. Since little information exists concerning the dietary effects of fusaric acid, the mycotoxin was mixed with feed at 10, 75, and 200 ppm and fed ad libitum to pregnant rats (F0 dams) from d 11–12 of gestation, through parturition and weaning (F1 generation). On d 4 postpartum, F1 pups were culled to 9–10 pups/litter; the stomach colostrum was collected from the culls and analyzed for fusaric acid. The mycotoxin in the colostrum (ng fusaric acid/100 mg colostrum) was directly related to the amount consumed by the nursing dams (i.e., 200 ppm pups, 3547 ng; 75 ppm pups, 1449 ng; 10 ppm pups, 80 ng; controls pups, 18 ng). All other animals survived, and appeared normal, healthy, and in good pelage. F0 dam feed consumption and dam and pup weights were not statistically different, but there was an inverse relation between pup average weight gain and amount of fusaric acid in the diets (i.e., weight gains: control pup > 10 ppm pup > 75 ppm pups > 200 ppm pups). At weaning, the F1 pups were randomly assigned to two groups per treatment: one group (F1A) for reproduction and fusaric acid effects on the F2 generation, and another group (F1B) for neurochemical comparisons. The F1A rats were maintained on their respective diets to age 13–14 wk; animals were bred (i.e., control males × control females, 10 ppm × 10 ppm, etc.) and the F1A dams and F2 pups were monitored as already described. Weight gains and fusaric acid in stomach colostrum from the F2-culls were analogous to the F1 generation. On d 5–6 and 7–8 postpartum, using litter weight gains as an indication of milk production in the F1 A dams (controls vs. 200 ppm), the controls gained 32.5% (p < .01) and 13.3% fp <.02), respectively, more than 200 ppm F2 pups. At weaning, no differences were observed in neurochemicals in the pineal gland for the F1 generation. However, in the F2 200 ppm male and female weanlings, fusaric acid decreased pineal serotonin (males, p <.001; females, p <.15) and tyrosine (males, p <.04; females, p <.07). The results indicate fusaric acid in diets at <0.3 ppm (i.e., background control diet) lactationally passes from nursing dams to the neonate; in weanlings, at 200 ppm, fusaric acid decreases pineal serotonin and tyrosine. The data also suggest limited neonate weight gains may be related to either decreased milk production in dams or mycotoxin effects on the neonate. This is the first report of fusaric acid's lactational passage from the feed of nursing dams to neonates and the oral suppression of pineal serotonin and tyrosine in offspring.

ISSN:0098-4108    

DOI:10.1080/00984108.1996.10662176

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor

摘要:

Exposure to the drinking water contaminant arsenate is a daily occurrence and there are concerns that this exposure may lead to cancer. Although the acute dispositional effects of arsenate have been studied in detail, there is minimal information on the disposition and toxicological effects of it after continuous exposure. The objective of this study was to examine in mice the effect of a 4-wk treatment with arsenate administered in drinking water. Female B6C3F1 mice (3/cage) were housed in metabolism cages and given water and food ad libitum. Two groups (A, B) of mice were treated (4 cages/treatment/group) with distilled water (control, C) or water containing 0.025 mg/L (L) or 2.5 mg/L (H) arsenate. Group A was sacrificed on d 28 and plasma and urine samples were taken for determination of clinical chemistry parameters. Liver and kidney tissue samples were taken for histopathological analysis. The reduced nonprotein sulfhydryl (NPSH) content in several tissues was determined. Group B was gavaged with [73As]arsenate on d 28 and continued the arsenate drinking water exposure for 48 h. Excreta and tissues were collected and analyzed for73As. Urine was further analyzed for arsenate and its metabolites. There were no effects on the mean daily amount of water and food consumed, whereas the mean daily urine volume excreted was significantly elevated by 10% in the H-treated animals compared to C and L. A dose-related hepatic vacuolar degeneration in the liver was observed, but no histological changes were evident in the kidney. Only clinical chemistry parameters in plasma were altered by the arsenate treatment. Glucose was significantly lower at the H dose compared to C and L, triglycerides were significantly greater in C than L and H, and creatinine was significantly greater in H than C. Hepatic NPSH content in the H animals was significantly lower than C and L animals, whereas no effects in lung and kidney were detected. The weights of liver, lung, and kidney, as well as their tissue/body weight ratios, were significantly decreased in the H animals.73As was primarily eliminated in urine, and its elimination was not affected by dose. No effects on the 48-h As cumulative excretion (urine + fecal) were detected. The73As distribution was low in amount and widely dispersed throughout the animal (<3% of the73As dose). The kidney had the highest As concentration of the tissues (0.01% As dose/g tissue). Dimethylarsinic acid was the major metabolite detected in urine, with lower amounts of arsenate, arsenite, and monomethylarsonate. There were no differences between the treatment groups in the amount of urinary metabolites after a single dose of [73As]arsenate. Several toxicological effects were observed in animals administered arsenate in drinking water, but no changes in the disposition of this arsenical were detected at the doses used in this study.

ISSN:0098-4108    

DOI:10.1080/00984108.1996.10662177

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor

摘要:

To understand the mechanism underlying the neurotoxicity of lithium ion, we investigated the inhibition of the nerve growth factor-induced neuronal differentiation of rat PCI2 pheochromocytoma cells induced by treatment with Lid. Incubation with 0.1–3 mMLiCI from 30 min before nerve growth factor (NCF) treatment attenuated neurite outgrowth. Moreover, incubation with 3 mMLiCI from 24 h before strongly reduced the neurite outgrowth. The chronic pretreatment inhibited the NCF-caused induction of acetylcholinesterase activity known to be elevated by NCF in transcription-dependent processes, and inhibited expression of c-fos proto-oncogene mRNA. This pretreatment also inhibited the NGF-induced formation of inositol phosphates, accompanied by the significant accumulation of inositol monophosphate. These observations, that chronic treatment with LiCI inhibits the NGF-induced neuronal differentiation in a transcription-dependent manner and inhibits phosphoinositide metabolism, suggest a possible causal relationship between these two events.

ISSN:0098-4108    

DOI:10.1080/00984108.1996.10662178

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor

摘要:

Clarified slurry oil (CSO, CAS number 64741-62-4), a refinery stream produced by processing crude oil, is a developmental toxicant when administered dermally throughout gestation to pregnant rats. The manifestations of developmental toxicity observed included embryolethality and growth retardation; evidence of teratogenicity was limited, and not conclusive. The present study was undertaken to further explore the teratogenic potential of CSO. In an attempt to limit embryolethality and thereby promote detection of terata, CSO was administered once daily for a limited period of gestation [gestation days (GD) 9–12], via dermal application, to pregnant Sprague-Dawley rats at doses of 0, 10, 100, and 1000 mg/kg. All animals were sacrificed on GD 20. Detailed examination of the dams was performed. Due to the screening nature of this investigation, fetal evaluations were limited to body weight measurements, external examinations, and evaluation of select visceral endpoints. In the dams exposed to CSO, significant decreases in body weight [absolute and gain (CD 9–13, CD 0–20)] and in the amount of food consumed were observed at 100 and 1000 mg/kg. Additional evidence of maternal toxicity observed at WOO mg/kg included decreased absolute and relative thymus weights, increased absolute and relative liver weights, and aberrant serum chemistry. Ingestion of the test material was evident at the high dose. Developmental toxicity was observed at 1000 mg/kg and included increased embryolethality, decreased body weight, and anomalous development (cleft palate, brachydactyly, edema). Although a low incidence of abnormal fetal development was observed at 100 mg/kg, it was not conclusive that the alterations were due to CSO exposure. It is likely that three- to seven-ring polycyclic aromatic compounds present in CSO were responsible for the toxic effects observed.

ISSN:0098-4108    

DOI:10.1080/00984108.1996.10662179

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/00984108.1996.10662172

出版商:Taylor & Francis Group    

年代:1996

数据来源: Taylor