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Mycotoxins, fungus and 'electrohypersensitivity'

MEDICAL HYPOTHESES 2000年第3期55卷 208-214页

作者： Anttila, K kimanttila@iobox.se

'Electrohypersensitivity' is often explained as a psychological syndrome. Our modern environment contains a lot of different substances and some of them are toxic. Mycotoxins are types of toxins that are biologically very active and that affect living organisms. Mycotoxins and fungi capable of producing toxins have been detected in ventilation systems, water damage and in foodstuff. Many of those displaying symptoms caused by electromagnetic fields have fungus infections or have been living in fungus-contaminated environments for long periods, In animal studies mycotoxins have shown the same effects as those seen in the 'electrohypersensitivity' syndrome. Phototoxic reactions are well known in veterinary medicine and in medical science, so the question is whether the 'electrohypersensitivity' syndrome is caused by 'phototoxic' reactions? (C) 2000 Harcourt Publishers Ltd.

关键词：消化系统/药物作用电磁场环境暴露眼/药物作用真菌/致病力真菌病/病理生理学真菌毒素类/分析真菌毒素类/毒性神经系统/药物作用皮肤/药物作用人类

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Hemolysis, toxicity, and randomly amplified polymorphic DNA analysis of Stachybotrys chartarum strains

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APPLIED AND ENVIRONMENTAL MICROBIOLOGY 1999年第7期65卷 3175-3181页

作者： Vesper, SJ Dearborn, DG Yike, I Sorenson, WG Haugland, RA US EPA Natl Exposure Res Lab Cincinnati OH 45268 USA Case Western Reserve Univ Rainbow Babies & Childrens Hosp Dept Pediat Cleveland OH 44106 USA NIOSH Div Resp Dis Studies Morgantown WV 26505 USA

Stachybotrys chartarum is an indoor air, toxigenic fungus that has been associated with a number of human and veterinary health problems. Most notable among these has been a cluster of idiopathic pulmonary hemorrhage cases that were observed in the Cleveland, Ohio, area. In this study, 16 strains of S, chartarum isolated from case (n = 8) or control (n = 8) homes in Cleveland and 12 non-Cleveland strains from diverse geographic locations were analyzed for hemolytic activity, conidial toxicity, and randomly amplified polymorphic DNA banding patterns, In tests for hemolytic activity, strains were grown at 23 degrees C on wet wallboard pieces for an 8-week test period. Conidia from these wallboard pieces were subcultured on sheep's blood agar once a week over this period and examined for growth and clearing of the medium at 37 or 23 degrees C. Five of the Cleveland strains (all from case homes) showed hemolytic activity at 37 degrees C throughout the 8-week test compared to 3 of the non-Cleveland strains. Five of the Cleveland strains, compared to two of the non-Cleveland strains, produced highly toxic conidia (>90 mu g of T2 toxin equivalents per g [wet weight] of conidia) after 10 and 30 days of growth on wet wallboard. Only 3 of the 28 strains examined both were consistently hemolytic and produced highly toxic conidia, Each of these strains was isolated from a house in Cleveland where an infant had idiopathic pulmonary hemorrhage.

关键词： DNA 细菌/分析疾病暴发流行溶血出血/微生物学住房肺疾病真菌性/流行病学肺疾病真菌性/微生物学真菌毒素类/毒性俄亥俄/流行病学种系发生聚合酶链反应随机扩增多态DNA技术葡萄穗霉属/分类葡萄穗霉属/遗传学葡萄穗霉属/分离和提纯葡萄穗霉属/致病力毒力人类婴儿婴儿新生

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Tremorgenic mycotoxins paxilline, penitrem and lolitrem B, the non-tremorgenic 31-epilolitrem B and electromyographic activity of the reticulum and rumen of sheep

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RESEARCH IN VETERINARY SCIENCE 1999年第2期66卷 119-127页

作者： McLeay, LM Smith, BL Munday-Finch, SC Univ Waikato Dept Sci Biol Hamilton New Zealand Pastoral Agr Res Inst Ltd Toxinol & Food Safety Res Grp Ruakura Res Ctr Hamilton New Zealand

The mycotoxic tremorgens penitrem, paxilline and lolitrem B had profound effects on electromyographic (EMG) activity of smooth muscle of the reticulorumen in conscious sheep, with a similar time course of action to their respective characteristic effects on the induction (1 to 2, 15 to 20 and 20 to 30 minutes) and the duration (1 to 2, 1 to 2 and 8 to 12 hours) of tremoring. Responses to penitrem revealed a greater sensitivity of smooth muscle than skeletal muscle. Effects included an inhibition of the vagally-dependent cyclical A and B sequences of contraction of the reticulorumen, an increase in their amplitude and an excitation of local intrinsic activity contributing to elevated baselines and the occurrence of chaotic activity of the reticulum. The excitatory local effects were partially blocked by atropine, indicating that stimulation of muscarinic cholinoceptors was involved. Increased local activity may mediate a reflex inhibition of cyclical contractions. A non-tremorgenic isomer of lolitrem B (31-epilolitrem B) had no effect on the reticulorumen. The intensity and duration of the effects of lolitrem B, up to 12 hours, indicate that severe disruption of digestion may occur in animals grazing endophyte-infected pasture.

关键词：阿托品/药理学肌电描记术吲哚类/毒性肌收缩/药物作用肌收缩/生理学肌平滑/药物作用肌平滑/神经支配肌平滑/生理学真菌毒素类/毒性睾丸切除术网状组织/药物作用网状组织/神经支配网状组织/生理学瘤胃/药物作用瘤胃/神经支配瘤胃/生理学绵羊迷走神经/生理学动物男(雄)性

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A longevity assurance gene homolog of tomato mediates resistance to Alternaria alternata f. sp lycopersici toxins and fumonisin B₁

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2000年第9期97卷 4961-4966页

作者： Brandwagt, BF Mesbah, LA Takken, FLW Laurent, PL Kneppers, TJA Hille, J Nijkamp, HJJ Free Univ Amsterdam Inst Mol Biol Sci Bioctr Amsterdam Dept Genet NL-1081 HV Amsterdam Netherlands

The phytopathogenic fungus Alternaria alternata f. sp, lycopersici (AAL) produces toxins that are essential for pathogenicity of the fungus on tomato (Lycopersicon esculentum). AAL toxins and fumonisins of the unrelated fungus Fusarium moniliforme are sphinganine-analog mycotoxins (SAMs), which cause inhibition of sphingolipid biosynthesis in vitro and are toxic for some plant species and mammalian cell lines. Sphingolipids can be determinants in the proliferation or death of cells. We investigated the tomato Alternaria stem canker (Asc) locus, which mediates resistance to SAM-induced apoptosis. Until now, mycotoxin resistance of plants has been associated with detoxification and altered affinity or absence of the toxin targets. Here we show that SAM resistance of tomato is determined by Asc-1, a gene homologous to the yeast longevity assurance gene LAG1 and that susceptibility is associated with a mutant Asc-1. Because both sphingolipid synthesis and LAG1 facilitate endocytosis of glycosylphosphatidylinositol-anchored proteins in yeast, we propose a role for Asc-1 in a salvage mechanism of sphingolipid-depleted plant cells.

关键词：衔接蛋白质类信号转导链格孢属/致病力氨基酸序列细胞凋亡羧酸类/毒性细胞死亡细胞分裂伏马菌素类真菌蛋白质类/化学真菌蛋白质类/遗传学 GTP结合蛋白质类基因植物番茄/药物作用番茄/遗传学番茄/微生物学膜蛋白质类/化学膜蛋白质类/遗传学分子序列数据真菌毒素类/毒性植物疾病/遗传学酿酒酵母蛋白质类序列比对序列同源性氨基酸鞘脂类/生物合成鞘脂类/代谢鞘氨醇/类似物和衍生物鞘氨醇/毒性

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Ochratoxin A induces JNK activation and apoptosis in MDCK-C7 cells at nanomolar concentrations

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JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS 2000年第3期293卷 837-844页

作者： Gekle, M Schwerdt, G Freudinger, R Mildenberger, S Wilflingseder, D Pollack, V Dander, M Schramek, H Inst Physiol D-97070 Wurzburg Germany Univ Innsbruck Dept Physiol A-6020 Innsbruck Austria

Ochratoxin A (OTA) is a ubiquitous fungal metabolite with nephritogenic, carcinogenic, and teratogenic action. Epidemiological studies indicate that OTA may be involved in the pathogenesis of different forms of human nephropathies. Previously we have shown that OTA activates extracellular signal-regulated kinases 1 and 2, members of the mitogen-activated protein kinases (MAPK) family, in the C7-clone but not in the C11-clone of renal epithelial Madin-Darby canine kidney (MDCK) cells. Here we show that nanomolar concentrations of OTA lead to activation of a second member of the MAPK family, namely, c-jun amino-terminal-kinase (JNK) in MDCK-C7 cells but virtually not in MDCK-C11 cells, as determined by kinase assay and Western blot. Furthermore, OTA potentiated the effect of tumor necrosis factor-alpha on JNK activation. In parallel to its effects on JNK, nanomolar OTA induced apoptosis in MDCK-C7 cells but not in MDCK-C11 cells, as determined by DNA fragmentation, DNA ladder formation, and caspase activation. In addition, OTA potentiated the proapoptotic action of tumor necrosis factor-alpha. Our data provide additional evidence that OTA interacts in a cell type-specific way with distinct members of the MAPK family at concentrations where no acute toxic effect can be observed. Induction of apoptosis via the JNK pathway can explain some of the OTA-induced changes in renal function as well as part of its teratogenic action.

关键词：细胞凋亡/药物作用细胞培养的剂量效应关系药物酶激活/药物作用丝裂原活化蛋白激酶8 丝裂原激活蛋白激酶类/药物作用丝裂原激活蛋白激酶类/代谢真菌毒素类/毒性赫曲霉毒素类/毒性磷酰化肿瘤坏死因子α/药理学动物狗

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A potential mechanism for fumonisin B₁-mediated hepatocarcinogenesis:: cyclin D1 stabilization associated with activation of Akt and inhibition of GSK-3β activity

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CARCINOGENESIS 2000年第8期21卷 1537-1546页

作者： Ramljak, D Calvert, RJ Wiesenfeld, PW Diwan, BA Catipovic, B Marasas, WFO Victor, TC Anderson, LM Gelderblom, WCA NCI Comparat Carcinogenesis Lab Frederick Canc Res & Dev Ctr Frederick MD 21702 USA US FDA Ctr Food Safety & Appl Nutr Off Special Nutr Div Sci & Appl Technol Laurel MD 20708 USA NCI Intramural Res Support Program SAIC Frederick Frederick Canc Res & Dev Ctr Frederick MD 21702 USA Johns Hopkins Univ Ctr Asthma & Allergy Baltimore MD 21224 USA S African MRC Nutr Dis Res Inst ZA-7505 Tygerberg South Africa Univ Stellenbosch MRC Ctr Cellular & Mol Biol ZA-7505 Tygerberg South Africa

Fumonisin B-1 (FB1) is a worldwide corn contaminant and has been epidemiologically linked to the high incidence of human esophageal cancer in South Africa and China. FB1 is hepatocarcinogenic in rats by an unknown mechanism. Inhibition of ceramide synthase and disruption of membrane phospholipids have been shown to be mechanisms of toxicity. Here we show overexpression of cyclin D1 protein in both preneoplastic and neoplastic liver specimens obtained from a long-term feeding study of FB1 in rats. In rats fed FB1 short-term, cyclin D1 protein levels in liver were increased up to five-fold in a dose-responsive manner. Northern blot analysis demonstrated no increase in mRNA levels of cyclin D1, 2D electrophoresis of cyclin D1 protein in FB1-treated samples showed a distinct pattern of migration (presence of less negatively charged form of the protein) that differed from controls. Recently, it has been shown that phosphorylation of cyclin D1 by glycogen synthase kinase 3 beta (GSK-3 beta) on a single threonine residue (Thr-286) positively regulates proteosomal degradation of cyclin D1, In FB1-treated samples we detected GSK-3 beta phosphorylated on serine 9;activated protein kinase B (Akt) appears to be responsible for this activity-inhibiting phosphorylation, These findings suggest that overexpression of cyclin D1 results from stabilization due to a lack of phosphorylation mediated by GSK-3 beta, We also observed an increase in cyclin dependent kinase 4 (Cdk4) complexes with cyclin D1 in FB1-treated samples;additionally, elevated Cdk4 activity was shown by increased phosphorylation of the retinoblastoma protein. In summary, the activation of Akt leads to increased survival, inhibition of GSK-3 beta activity and post-translational stabilization of cyclin D1, all events responsible for disruption of the cell cycle G(1)/S restriction point in hepatocytes, This is the first report suggesting the mechanism by which FB1 acts as a carcinogen.

关键词：钙-钙调素依赖性蛋白激酶类/拮抗剂和抑制剂钙-钙调素依赖性蛋白激酶类/代谢羧酸类/毒性致癌物环境/毒性细胞周期蛋白D1/生物合成细胞周期蛋白D1/代谢细胞周期蛋白依赖激酶4 细胞周期蛋白质依赖激酶类/代谢酶激动剂类/毒性伏马菌素类 G1期/药物作用 G1期/生理学基因表达调控肿瘤基因 ras/遗传学糖原合成酶激酶3 糖原合成酶激酶类肝/药物作用肝/酶学肝/代谢肝肿瘤实验性/化学诱导肝肿瘤实验性/酶学肝肿瘤实验性/代谢突变真菌毒素类/毒性癌前状态/化学诱导癌前状态/酶学癌前状态/代谢蛋白质加工转译后/药物作用蛋白质丝氨酸苏氨酸激酶原癌基因蛋白质类/代谢原癌基因蛋白质c-akt 大鼠近交F344 S期/药物作用 S期/生理学动物大鼠

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Cluster organization and pore structure of ion channels formed by beticolin 3, a nonpeptidic fungal toxin

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BIOPHYSICAL JOURNAL 1999年第6期77卷 3052-3059页

作者： Goudet, C Benitah, JP Milat, ML Sentenac, H Thibaud, JB Univ Montpellier 2 Lab Biochim & Physiol Mol Plantes CNRS URA 2133ENSAMINRA F-34060 Montpellier 1 France Univ Bourgogne Lab Phytopharm & Biochim Interact Cellulaires UA 692 INRA F-21034 Dijon France

Beticolin 3 (B3) belongs to a family of nonpeptidic phytotoxins produced by the fungus Cercospora beticola, which present a broad spectrum of cytotoxic effects. We report here that, at cytotoxic concentration (10 mu M), B3 formed voltage-independent, weakly selective ion channels with multiple conductance levels in planar lipid bilayew. In symmetrical standard solutions, conductance values of: the first levels were, respectively, 16 +/- 1 pS, 32 +/- 2 pS, and 57 +/- 2 pS (n = 4) and so on, any conductance level being roughly twice the lower one. Whether a cluster organization of elementary channels or different channel structures underlies this particular property was addressed by investigating the ionic selectivity and the pore size corresponding to the first three conductance levels. Both selectivity and pore size were found to be almost independent of the conductance level. This indicated that multiple conductance behavior resulted from a cluster organization of "B3 elementary channels." According to the estimated pore size and analyses of x-ray diffraction of B3 microcrystals, a structural model for "B3 elementary channels" is proposed. The ability to form channels is likely to be involved in the biological activity of beticolins.

关键词：生物物理学导电性离子通道/化学离子通道/药物作用脂双层膜电位模型分子分子构象真菌毒素类/化学真菌毒素类/毒性

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MYCOTOXICOSIS PRODUCED IN MICE BY CULTURAL PRODUCTS OF AN ISOLATE OF ASPERGILLUS-OCHRACEUS

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FOOD AND COSMETICS TOXICOLOGY 1976年第6期14卷 571-+页

作者： ZIMMERMANN, JL CARLTON, WW TUITE, J PURDUE UNIV SCH VET MED DEPT VET MICROBIOL & PATHOL W LAFAYETTE IN 47907 USA PURDUE UNIV SCH AGR DEPT BOT & PLANT PATHOL W LAFAYETTE IN 47907 USA

An isolate of A. ochraceus was examined for toxicity in male and female Swiss albino mice fed diets containing rice culture and ground fungal mats. The ground rice culture was mixed with a commercial purified diet at concentrations of 5, 7.5, 9, 10, 25 and 50% and the fungal mats at concentrations of 1, 2 and 3%. In groups fed the fungal-mat diet, body-weight gains were markedly reduced and in those fed the highest concentrations approximately half the mice died. Nearly all the mice fed the rice-culture diets had died by the 3rd wk of feeding. The 3 wk LD50 was about 7.0% for both sexes of mice fed the rice culture and 2.3% for those fed the fungal mats. Gross lesions with both types of diet included jaundice, greenish discoloration of the kidneys and focal necrosis in the liver. Microscopically, the earliest changes occurred in the biliary ducts and included necrosis of the epithelium, periductal edema, infiltration of inflammatory cells, periductal fibrosis and disseminated focal necrosis of hepatic cells. The necrotizing and inflammatory changes also involved the extrahepatic bile ducts. Lesions in the kidneys consisted of tubular necrosis and biliary casts within the convoluted tubules and collecting ducts.

关键词：曲霉菌属/代谢胆管/药物作用胆管/病理学血细胞计数体重/药物作用胆管炎/化学诱导胆管炎/病理学培养基膳食胆囊/药物作用胆囊/病理学肾/药物作用肾/病理学半数致死量肝/药物作用肝/病理学真菌毒素类/生物合成真菌毒素类/毒性坏死胰腺/药物作用胰腺/病理学胰腺炎/化学诱导胰腺炎/病理学动物女(雌)性男(雄)性小鼠

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INTERACTION OF T-2 TOXIN WITH SALMONELLA INFECTIONS OF CHICKENS

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POULTRY SCIENCE 1975年第5期54卷 1693-1696页

作者： BOONCHUVIT, B HAMILTON, PB BURMEISTER, HR N CAROLINA STATE UNIV DEPT POULTRY SCIRALEIGHNC 27607 USDA NO REG RES LABPEORIAIL 61604 N CAROLINA STATE UNIV DEPT MICROBIOLRALEIGHNC 27607

A significant (P less than 0.05) interaction resulting in increased mortality occurred in chickens fed T-2 toxin (16 mug./g. of diet) and infected with either Salmonella worthington, S. thompson, S. derby, or S. typhimurium var. copenhagen, all species that cause paratyphoid. No interaction on growth rate or relative size of the bursa of Fabricus occurred, although T-2 toxin alone caused a significant (P less than 0.05) regression of that organ. The spleen size relative to the body weight was decreased (P less than 0.05) by T-2 toxin and increased (P less than 0.05) by the Salmonella infections. Interactions were observed on spleen size between the toxin and S. thompson (P less than 0.05) and S. derby (P less than 0.10). Total serum proteins were not affected by T-2 toxin or Salmonella infections. Agglutinins were formed in response to the infections, but the titers were unaltered by T-2 toxin.

关键词：血蛋白质类/分析醚类/药理学镰刀菌属真菌毒素类/药理学真菌毒素类/毒性家禽疾病/化学诱导家禽疾病/死亡率沙门菌属沙门菌感染动物/并发症沙门菌感染动物/死亡率鼠伤寒沙门菌倍半萜类/毒性脾/药物作用单端孢霉烯类/药理学单端孢霉烯类/毒性动物男(雄)性

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SHORT-TERM PERORAL TOXICITY OF ETHYLIDENE GYROMITRIN IN RABBITS AND CHICKENS

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FOOD AND COSMETICS TOXICOLOGY 1976年第5期14卷 409-415页

作者： NISKANEN, A PYYSALO, H RIMAILAPARNANEN, E HARTIKKA, P TECH RES CTR FINLAND FOOD RES LAB SF-02150 ESPOO 15 FINLAND COLL VET MED HELSINKI DEPT PATHOL SF-00550 HELSINKI 55 FINLAND

Ethylidene gyromitrin, the main toxic compound in false morel (Gyromitra esculenta), was given in drinking-water to groups of 5 rabbits and 10 chickens of each sex in doses of 0 (control), 0.05, 0.5 or 5.0 mg/kg per day for 90 days. The following tests and measurements were made during this period or at autopsy: weight increase, relative organ weights, hematological measurements, serum and urine analyses, including the determination of ethylidene gyromitrin in the urine, and macro- and histopathological examination. The no-effect level of ethylidene gyromitrin was estimated as 0.5 mg/kg per day for rabbits and 0.05 mg/kg per day for chickens. The most important biological effects in rabbits were degenerative changes in the tubular cells of the kidneys, while in chickens defects were also detected in the heart muscle and liver parenchymal cells.

关键词：乙醛/类似物和衍生物乙醛/毒性体重/药物作用鸡腙类/毒性真菌毒素类/毒性器官测量/药物作用时间因素动物女(雌)性男(雄)性兔

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