摘要:

AbstractThe cyanobacterial toxin microcystin‐LR (MCLR) is a potent inhibitor of protein phosphatases 1 and 2A, and is selectively toxic to the liver in vivo and to isolated hepatocytes in vitro. This selectivity is believed to be due to toxin uptake via bile acid carriers. We investigated at the light and ultrastructural levels the effects of high concentrations of MCLR and long incubation times to determine in vitro whether fibroblasts and kidney cells (non‐target cells) respond in the same manner as do hepatocytes (target cells) at low concentrations and short incubation times. Cultured rat skin fibroblasts (ATCC 1213) and rat kidney epithelial cells (ATCC 1571) were incubated with MCLR at 133 μM 1‐24 hr. Lesions in these cells were compared with those in cultured hepatocytes incubated with MCLR at 13.3 μM from 1 to 32 min. Lesions in hepatocytes, kidney cells, and fibroblasts were noted at 4 min, 1 hr, and 8 hr, respectively, after initial exposure to MCLR. Lesions in all three cell types progressed and included plasma membrane blebbing, loss of cell‐to‐cell contact, clumping and rounding of cells, cytoplasmic vacuolization, and redistribution of cytoplasmic organelles. Loss of microvilli, whorling of rough endoplasmic reticulum, dense staining and dilated cristae in mitochondria, and pinching off of membrane blebs were noted only in hepatocytes. Nuclear changes typical of apoptosis were observed only in fibroblasts and kidney cells. Similarities in responses of different cell types to MCLR exposure probably reflect a common biochemical mechanism of action, i.e., inhibition of protein phosphatases 1 and 2A as described by others. The observed differences in the responses of the cell types examined in this study may reflect differences in the proteins phosphorylated and the severity of hyperphosphorylation. © 1995 Wil

ISSN:1056-9014    

DOI:10.1002/nt.2620030302

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractBased on the DNA fragmentation profile in gel electrophoresis and the morphological changes in electron microscopy, the induction of apoptotic nuclear changes by mycotoxins and other microbial products, in total 31 chemicals, was investigated in HL‐60 human promyelotic leukemia cells, along with the cytotoxicity tests with 3‐[4,5‐dimethylthiazol‐zyl]‐2,5‐diphenyltetrazolium bromide (MTT) and trypan blue exclusion. Among the chemicals tested, trichothecenes (T‐2 toxin, roridin A, nivalenol, deoxynivalenol), certain anthraquinones (luteoskyrin, skyrin, 2‐hydroxyemodin), diketopiperazines (emethallicin A, emestrin), isocoumarins (ochratoxin A, citrinin), lactone (penicillic acid), dihydrobisfuran (aflatoxin B), potassium ionophore (valinomycin), and an inhibitor of interleukin‐2 synthesis (cyclosporin A) were positive for the induction of DNA fragmentation. No DNA fragmentation was observed under the present conditions with fumonisin B1, cyclic peptides (cyclochlorotine, phalloidin, microcystin‐LR), certain anthraquinones (emodin, chrysophanol, rugulosin), and others (sterigmatocystin, cytochalasin A, griseofulvin, fusaric acid, kojic acid, rubratoxin B, butenolide, wortmannin, FK506, and sphingosine). The apoptotic changes in the cells exposed to T‐2 toxin and luteoskyrin were confirmed by electron microscopic observation. Detailed experiments on dose and time dependencies revealed that T‐2 toxin induced the apoptosis at 10 ng/ml (= 4 × 10‐8M) levels within 2‐6 hr without significant cytotoxicity evaluated by the dye exclusion and

ISSN:1056-9014    

DOI:10.1002/nt.2620030303

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe Fusarium mycotoxin zearalenone (ZEA), added at a level of 2 μ/ml, was reduced stereoselectively by cultures of Candida tropicalis, Torulaspora delbrückii, Zygosaccharomyces rouxii, and 7 Saccharomyces strains to both α‐ and β‐zearalenol. In contrast, only a‐zearalenol was produced from ZEA by Pichia fermentans and several yeast strains of the genera Candida, Hansenula, Brettanomyces, Schizosaccharomyces, and Saccharomycopsis. No glucose conjugates of ZEA (zearalenone‐4‐β‐D‐glucopyranoside) were detected. The trichothecene mycotoxin deoxynivalenol (DON) was not metabolized by any of the yeast strains that were used for analysis. © 1

ISSN:1056-9014    

DOI:10.1002/nt.2620030304

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe mycotoxin fumonisin B1(FB1) was dosed as14C‐labelled FB1to male vervet monkeys (Cercopithecus aethiops) both by intravenous (iv) injection (2 monkeys, dose 1.72 mg [86 kBq]/kg body weight) and by gavage (2 monkeys, dose 6.42 mg [321 kBq]/kg body weight). Excreta were collected over a 24‐hr period, whereafter the monkeys were sacrificed and selected organs and contents of the gut collected to determine the distribution of the14C‐label. The bulk of the radioactivity recovered from tissue was found in the liver (mean of 1.92% in iv‐dosed monkeys; 0.64% in gavage‐dosed monkeys). Of the other organs analysed, the following mean amounts of radioactivity were recovered in organs of iv‐ and savage‐dosed monkeys, respectively: muscle, 0.62% and 0.14%; kidney, 0.37% and 0.03%; brain, 0.08% and 0.02%; lung, 0.07% and 0.03%; heart, 0.04% and 0.01%; spleen, 0.02% and<0.01%; plasma, 0.66% and 0.12%; red blood cells, 0.11% and 0.01%; while a further 68.1% and 64.0% were recovered in excreta, bile, and the gut contents. Analysis of faeces and gut contents showed that radioactivity was due to FB1, its partially hydrolysed metabolites, and trace amounts of the fully hydrolysed aminopentol moiety. Analysis of bile showed an absence of hydrolysis products, indicating that hydrolysis occurred only in the gut, resulting in the removal of the tricarballylic acid moiety at the C14‐position. Determination of FB1levels in plasma following a gavage dose indicated that only limited amounts of FB1were absorbed, as plasma levels peaked after 1‐2 hr with levels below 210 ng/ml. © 19

ISSN:1056-9014    

DOI:10.1002/nt.2620030305

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractUsing the method of bilayer membranes at the tip of a patch pipette, the properties of the ionic channels produced by the ionophore toxin pardaxin were investigated. At low toxin concentrations, voltage‐dependent, single‐channel events were measured. The current‐voltage curves were non‐linear when determined in Tris‐CI solution, but were linear in K+‐HEPES solution. Using asymmetric ion solutions, the ionic selectivity of pardaxin channels was estimated from the reversal potentials obtained. The sequence of the relative permeabilities for monovalent cations was Tl+>Rb+>Cs+>K+,NH4+>methylamine+>Li+>dimethylamine+>Na+. Except for Li+, the selectivity sequence fitted the cations relative hydrated size. For bivalent ions the permeability of Ba2+, Sr2+, and Mn2+relative to Mg2+changed according to the relative hydrated size. For anions the selectivity sequence was I−>NO3−>Br−>CI−>CIO4−>SCN−>BF−>HCOO−>F−>CH3COO−. The selectivity sequence for the small anions (I−, NO3−, Br−, CI−) was different from their hydrated size. Pardaxin channel showed a modest ion selectivity between small anions and cations (PK:PCI:PNa= 1.28:1.00:0.56). Pardaxin is proposed as a biophysical model to study ionic chan

ISSN:1056-9014    

DOI:10.1002/nt.2620030306

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractCyclopaldic acid (CA), its six derivatives, and iso‐cyclopaldic acid (IsoCA) were assayed for toxicity to cuttings of three species of cypress, as well as to mung bean, oat, and tomato explants. Toxicity to host and non‐host plants of CA derivatives having one or both of the aldehyde groups transformed was less than that of CA. Shoot tissues of Cupressus macrocarpa artificially infected by Seiridium cupressi leached electrolytes more than those of C. sempervirens and C. arizonica. CA, IsoCA, and to a lesser extent the monoacetylated, phenylhydrazone and hydrogenated derivatives of CA caused loss of electrolytes from cypress tissures. CA, IsoCA, and monoacetyl CA caused limited callus development of cypress tissue. Diacetylhydrazone CA enhanced the yield of cypress callus tissue. CA derivatives having both aldehyde groups modified induced root formation on cypress cuttings. The antifungal activity showed by CA toward species of Botrytis, Fusarium, and Geotrichum markedly decreased in its derivatives. The inhibitory effect of CA on esterases was exhibited also by IsoCA and the monoacetylated derivative. © 1995 Wiley‐Lis

ISSN:1056-9014    

DOI:10.1002/nt.2620030307

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe phytotoxins seiridin (SEI) and iso‐seiridin (ISE), two Δαβ‐butenolides produced in vitro by Seiridium cardinale, S. cupressi, and S. unicome, as well as their derivatives obtained by chemical modification of each toxin, were analyzed for their bioactivity. The effects of each compound on host and non‐host plants and their antimicrobial activity on bacteria were investigated. The toxicity of both seiridins (SEIs) decreased in the derivatives with modifications of the γ‐lactone ring or with acetylation of the hydroxy group of the aliphatic side chain at C‐4. Shoot tissues of Cupressus macrocarpa artificially infected by S. cardinale leached electrolytes more than those of C. sempervirens and C. arizonica. Electrolyte loss from shoot tissues of cypress plants treated with each derivative also decreased for most of them. Seed germination was not affected by SEI and ISE derivatives. Inhibition of root growth of three herbaceous test plants was studied. SEI and 3,4‐dihydro SEI were active to germlings of lettuce. No ISE derivative affected root growth of lettuce and oat germlings. Reduction was observed on roots of radish germlings treated with acetyl ISE or 3,4‐dihydro ISE. No derivative of SEI or ISE elicited hormone‐like activity as SEI did. Antibacterial activity shown by SEI and ISE at 150 μM accounted for both hydrogenated derivatives of SEI. The integrity of the Δαβ‐unsaturated‐γ‐lactone ring and the location of the hydroxy group in the heptyl side chain are features of importance in biological activity of the two buteno

ISSN:1056-9014    

DOI:10.1002/nt.2620030308

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

摘要:

AbstractHorses grazins for prolonged periods on yellow star thistle (YST), a plant which grows wild in western parts of the United States, develop an extrapyramidal disorder known as nigropallidal encephalomalacia (NPE). Attempts have been made to identify, isolate, and characterize the toxins responsible for the disease in animals. Using the organotypic tissue culture system on mouse cortical explants as a specific assay method for neurotoxicological evaluation, it has been possible to isolate and characterize two potent neuroexcitotoxic compounds, aspartic and glutamic acids, the former being the major toxic component in the alcoholic extract of the plant. There is also evidence that other neurotoxic compounds are present in the extract. The detailed procedure for isolation and characterization of these compounds is given here. © 1995 Wiley‐Liss, I

ISSN:1056-9014    

DOI:10.1002/nt.2620030309

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY

ISSN:1056-9014    

DOI:10.1002/nt.2620030301

出版商:John Wiley&Sons, Inc.    

年代:1995

数据来源: WILEY