摘要:

Chronic arsenic exposure is associated with alterations in peripheral circulation and vascular disease. Toxicity to the vasculature is documented, but the effect of arsenic on the erythrocyte has not been evaluated. To determine if arsenic was toxic to human erythrocytes and whether this could contribute to vascular disease, human erythrocytes were incubated in vitro with sodium arsenate, As(V), or sodium arsenite, As(III), and assessed for damage. After 5 h of incubation with 10 m M As(V) or As(III), significant cell death (hemolysis) only occurred in the As( V) treated cells. Morphologic changes were assessed by scanning electron microscopy and light microscopy. As(V) induced a classic discocyte-echinocyte transformation extending to the formation of sphero-echinocytes; these changes were concentration dependent. As(III) treatment also resulted in echinocyte formation but less extensive than in As(V) treated cells, and no spheroechinocytes were formed. The observed damage was consistent with reported changes induced by ATP depletion, and measurement of ATP in these samples confirmed this as a mechanism of damage. As(V) treatment at concentrations as low as 0.01 m M for 5 h significantly depleted ATP, and As(III) was relatively ineffective in causing ATP depletion. Based on these three parameters, the erythrocyte was estimated to be as much as 1000 times more susceptible to As(V) than As(III). ATP is required for the cell to maintain membrane integrity and deform efficiently in circulation. The changes described here could contribute to vascular occlusion, ischemia, and tissue death associated with arsenic circulatory disorders.

ISSN:1528-7394    

DOI:10.1080/009841098159213

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

The heavy metal lead (Pb) markedly augments the lethality of endotoxin in laboratory animals. Much of the tissue injury produced by endotoxin is thought to be mediated by cytokines. Thus, the effects of Pb on the regulation of interleukin-6 (IL-6), a proinflammatory cytokine that shows high correlation with symptoms of endotoxic shock, and the levels of corticosterone, a hormone produced to prepare the body to cope with stress, upon lipopolysaccharide (LPS; endotoxin) administration were investigated. After intravenous administration of LPS, the kinetics of IL-6 gene expression by Northern blot analysis revealed a rapid increase of IL-6 mRNA, which peaked by 2 h in the spleens and 3 h in the brains of B6C3F1 female mice, with or without Pb exposure. Peak production of IL-6 protein after LPS challenge was observed at 2 h in the spleens and 3 h in the sera regardless of Pb-treatment. However, Pb-exposed mice showed an altered kinetic profile of IL-6 appearance in the brain, in that the levels of IL-6 in the brains peaked at 4 h rather than 3 h, the peak for the control mice. Moreover, at two time points, the amounts of IL-6 were found to be higher in the brains of Pb-treated mice. Increases in IL-6 were detected in multiple areas of the brain, but Pb did not significantly enhance this level in any area. The observation of both IL-6 transcripts and protein in the brains of mice upon peripheral LPS administration is indicative of local de novo synthesis of IL-6 in the brain. IL-6 production in the brain may contribute to the centrally mediated effects of IL-6, since IL-6 in the brain is known to activate the hypothalamus-pituitary-adrenal (HPA) axis. Upon LPS challenge, corticosterone levels peaked at the 2-h time point and stayed elevated for 6 h regardless of Pb exposure. The increases in brain IL-6 and its extended expression by Pb do not appear to have significantly altered the HPA axis on the basis of the corticosterone level, but brain IL-6 is known to affect multiple brain functions such as long-term potentiation.

ISSN:1528-7394    

DOI:10.1080/009841098159222

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

Adult male Sprague-Dawley rats were fed 70 mg/ kg body weight chlorogenic acid (CHA) for 7 wk. One CHA-fed group was also given 2 injections of the colon carcinogen azoxymethane (AZO) on d 2 and 9 of CHA treatment. Three major types of immune responses were assessed: antibody production, specific cell-mediated immunity, and nonspecific cell-mediated immunity. The formation of AZO-induced aberrant crypt foci (ACF) in the colon were observed, as was colonic cell proliferation. There were no significant effects of CHA treatment on any of the immune parameters examined or on formation of preneoplastic lesions or cell proliferation in the colon. The overall nonsignificant trends in immune function, colon cell proliferation, and ACF development were, however, more consistent with immunosuppression and enhanced preneoplasia.

ISSN:1528-7394    

DOI:10.1080/009841098159231

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

Carboxylesterases (CbxE) can be inhibited by organophosphorus esters (OPs) without causing clinical evidence of toxicity. CbxE are thought to protect the critical enzyme acetylcholinesterase (AChE) from OP inhibition in animals. CbxE and AChE are both present in neuroblastoma cells, but, even though these cells have potential to be an in vitro model of OP toxicity, the effect of OPs on CbxE and the relationship of CbxE inhibition and AChE inhibition have not yet been examined in these cells. Therefore, this study examined concentration-related OP-induced inhibition of CbxE in human SHSY5Y and mouse NB41A3 neuroblastoma cells with 11 active esterase inhibitors: paraoxon, malaoxon, chlorpyrifos-oxon, tolyl saligenin phosphate (TSP), phenyl saligenin phosphate (PSP), diisopropyl phosphorofluoridate (DFP), mipafox, dichlorvos, trichlorfon, dibutyryl dichlorovinyl phosphate (DBVP), and dioctyl dichlorovinyl phosphate (DOVP). All could inhibit CbxE, although the enzyme was less likely to be inhibited than AChE following exposure to 9 of the test compounds in the human cell line and to all 11 of the test compounds in the murine cell line. Species differences in concentration-related inhibitions of CbxE were evident. When cells were exposed first to an OP with a low IC50 toward CbxE (PSP), followed by an OP with high affinity for AChE (paraoxon or malaoxon), inhibitions of CbxE and AChE were additive. This indicated that CbxE did not protect AChE from OP-induced inhibition in this cell culture model.

ISSN:1528-7394    

DOI:10.1080/009841098159240

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor

摘要:

In view of the methodological problems of epidemiological studies on associations between residential and occupational exposures to 50/ 60-Hz magnetic fields (MF) and increased incidence of cancers, laboratory studies are necessary to determine if 50/60-Hz MF can affect cancer development or growth. Recently, it was reported that alternating (50-Hz) MF of low flux density (100 muT) increase tumor growth and progression in a model of breast cancer in female rats in which mammary tumors were induced by the chemical carcinogen 7,12-dimethylbenz\[a]anthracene (DMBA). The objective of the present study was to determine if a replicate experiment carried out in the same laboratory under the same experimental conditions yields a significant increase in tumor development and growth of similar magnitude. For the MF experiment, a group of 99 female Sprague-Dawley rats was exposed to a homogeneous horizontally polarized MF for 24 h/ d (minus time for weighing, tumor palpation, cage cleaning, cage rotation), 7 d/wk; another group of 99 rats was sham exposed. DMBA was administered intragastricly at a dose of 5 mg/ rat at the first day of exposure and at weekly intervals thereafter up to a total dose of 20 mg/ rat. Duration of MF or sham exposure was 91 d. In both MF-exposed and sham-exposed rats, the first tumors could be recorded 6 wk after the initial DMBA application. At 9 wk after DMBA application, the group of MF-exposed rats exhibited significantly more animals with tumors than the sham-exposed group. This significant difference in the rate of tumor development was observed throughout the subsequent period of exposure. After autopsy, the incidence of macroscopically visible mammary tumors was 62% in controls, but 83% in MF-exposed rats, with the 35% difference between groups being statistically significant. Data substantiate that long-term exposure of DMBA-treated female Sprague-Dawley rats in an alternating MF of low flux density promotes the development and growth of mammary tumors, thus indicating that MF exposure exerts tumor-promoting and/or copromoting effects. Furthermore, the data show that the effects of MF exposure in the DMBA breast cancer model are reproducible if the same experiment is repeated in the same laboratory.

ISSN:1528-7394    

DOI:10.1080/009841098159259

出版商:Informa UK Ltd    

年代:1998

数据来源: Taylor