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Biomedical subjects

M E Stack

Publications and source records attributed to M E Stack.

At least 19 recordsLinked to original sources
PubMed2001

Species- and sex-specific renal cytotoxicity of ochratoxin A and B in vitro.

Four different cell models were chosen for comparison of OTA and OTB toxicity: primary porcine (PKC), rat (RPTC) and human renal proximal epithelial cells (HKC) from both sexes and a porcine renal cell line: LLC-PK1. Culture conditions were tested and optimized for each respective cell type (species/sex and origin). All cell types were characterized for epithelial origin and growth patterns and following optimization of dosing strategies and assay procedures, a strict study design was implemented to avoid systemic variations. Due to possible sensitivity differences, three simple endpoints were chosen to provide basic data for interspecies comparison: neutral red uptake, MTT reduction and cell number. Of the endpoints tested neutral red appeared the most sensitive, although all three parameters yielded comparable EC50's. Sex-differences were observed between male and female HKC cells following 96 h exposure to OTA, with HKC(m) being more sensitive than HKC(f). No sex-difference was observed in PKC cells, however, the PKC were approximately 3 and 10 times more sensitive than HKC(m) and HKC(f), respectively, to OTA and OTB. Interestingly, the CI95 of the EC50 values obtained for OTA (15.5-16.5 microM) and OTB (17.0-2 1.0 microM) were comparable in the PKC cells. In contrast, OTB had lower cytotoxicity than OTA in HKC and LLC-PK1 (approx. 2-fold) and no effects in RPTC. Overall, HKC(m) were nearly as sensitive as PKC towards OTA, followed by RPTC, LLC-PK1 and HKC(f), thus suggesting a sex specific sensitivity in humans towards OTA induced cytotoxicity.

Animals↗
PubMed2001

Fumonisin b1 carcinogenicity in a two-year feeding study using F344 rats and B6C3F1 mice.

Fumonisin B1 (FB1) is a mycotoxin isolated from Fusarium fungi that contaminate crops worldwide. A previous study demonstrated that FB1 promoted preneoplastic foci in initiated rats and induced hepatocellular carcinomas in BD IX rats at 50 parts per million (ppm), but fundamental dose-response data were not available to assist in setting regulatory guidelines for this mycotoxin. To provide this information, female and male F344/N/Nctr BR rats and B6C3F1 Nctr BR mice were fed for two years a powdered NIH-31 diet containing the following concentrations of FB1: female rats, 0, 5, 15, 50, and 100 ppm; male rats, 0, 5, 15, 50, and 150 ppm; female mice, 0, 5, 15, 50, and 80 ppm; male mice, 0, 5, 15, 80, and 150 ppm. FB1 was not tumorigenic in female F344 rats with doses as high as 100 ppm. Including FB1 in the diets of male rats induced renal tubule adenomas and carcinomas in 0/48, 0/40, 9/48, and 15/48 rats at 0, 5, 15, 50, and 150 ppm, respectively. Including up to 150 ppm FB1 in the diet of male mice did not affect tumor incidence. Hepatocellular adenomas and carcinomas were induced by FB1 in the female mice, occurring in 5/47, 3/48, 1/48, 19/47, and 39/45 female mice that consumed diets containing 0, 5, 15, 50, and 80 ppm FB1, respectively. This study demonstrates that FB1 is a rodent carcinogen that induces renal tubule tumors in male F344 rats and hepatic tumors in female B6C3F1 mice.

Animal Feed↗
PubMed2001

Production of alternariol and alternariol methyl ether by Alternaria alternata grown on fruits at various temperatures.

Two toxigenic strains of the fungus Alternaria alternata (ATCC 56836 and ATCC 66868) were grown on surface-disinfected, fresh, ripe fruits and tested for the production of alternariol (AOH) and alternariol methyl ether (AME). Examined fruits included strawberries; red and green seedless grapes; concord grapes; red delicious, golden delicious, and gala apples; and blueberries. After inoculation, fruits were incubated at 4, 10 degrees C, or room temperature (approximately 21 degrees C) for up to 3 weeks. At weekly intervals, duplicate samples were analyzed for AOH and AME by using liquid chromatography. Results indicated that A. alternata and its metabolites were not a major problem in strawberries due to the presence of fast-growing molds like Rhizopus and Botrytis that outgrew and possibly inhibited Alternaria. Both Alternaria strains showed limited growth on apples, although fast-growing molds were not present after surface disinfection; AOH and AME were produced only by the ATCC 56836 strain on the golden delicious and gala varieties, (ranging from <0.1 to 5 microg/g and <0.1 to 14 microg/g for AOH and AME, respectively). Restricted growth of both strains without toxin production occurred in blueberries, whereas moderate growth and AOH (<0.1 to 3,336 microg/g) and AME (<0.1 to 1,716 microg/g) production took place in grapes.

Alternaria↗
PubMed1997

Assessment of the embryotoxic potential of the total hydrolysis product of fumonisin B1 using cultured organogenesis-staged rat embryos.

Aminopentol (AP1) is the total hydrolysis product of fumonisin B1 (FB1), the major and best characterized of the fumonisins, which are mycotoxins that are common contaminants of corn and corn meal. Some human populations expected to have significant exposure to AP1 have a high incidence of babies born with neural tube defects (NTD). The embryotoxicity of AP1 was evaluated in cultured rat embryos. Gestation day 9.5 embryos were exposed to 0, 3, 10, 30, 100 or 300 microM AP1 throughout the entire 45-hr culture period. At 100 microM AP1, growth and overall development were reduced significantly. There was also a significant increase in the incidence of abnormal embryos. 29% of the embryos had NTD, and 36% of the embryos had other abnormalities. At 300 microM AP1, the incidence of NTD was 15%, and 85% of the embryos had other abnormalities. These findings suggest that AP1, at concentrations of 100 microM and above, can induce NTD in organogenesis-stage cultured rat embryos. However, these NTD are in conjunction with significant overall retardation of growth and development as well as significant increases in the incidence of other defects. These studies also showed, when compared with previous findings, that AP1 is over 100-fold less toxic than FB1 to cultured rat embryos.

Abnormalities, Drug-Induced↗
PubMed1994

Evaluation of alternariol and alternariol methyl ether for mutagenic activity in Salmonella typhimurium.

Alternariol and alternariol methyl ether were tested in the Ames Salmonella typhimurium assay, and both were shown, with and without metabolic activation, to be nonmutagenic to strains TA98 and TA100. The finding of other investigators that alternariol methyl ether is weakly mutagenic to TA98 without metabolic activation could have resulted from the presence of a small amount of one of the highly mutagenic altertoxins in the alternariol methyl ether originally tested.

Animals↗
PubMed1991

Mutagenicity of stemphyltoxin III, a metabolite of Alternaria alternata.

Some common decay organisms of vegetables and ripened fruits are Alternaria species. Even fruits and vegetables kept under refrigeration can be spoiled by Alternaria species because the mold grows at low temperatures. Alternaria alternata is commonly found in grain in areas with a high incidence of esophageal cancer. Three metabolites, altertoxins I, II, and III, have been isolated from A. alternata and have hydroxyperylenequinone structures. Although other perylenequinone metabolites such as stemphyperylenol and stemphyltoxins I, II, III, and IV, have been isolated from Stemphylium botryosum var. lactucum, a plant pathogen and mold, we isolated and identified stemphyltoxin III from A. alternata. This metabolite was tested for mutagenicity in the Ames Salmonella typhimurium plate incorporation assay with and without Aroclor 1254-induced rat S-9 metabolic activation. A positive response was noted with and without metabolic activation in S. typhimurium TA98 and TA1537, and there was a marginal response in strain TA100.

Alternaria↗
PubMed1989

Photodynamic production of superoxide in vitro by altertoxins in the presence of reducing agents.

Superoxide production by the three 4,9-dihydroxyperylene-3,10-quinone fungal toxins, altertoxins I, II, and III, was stimulated on illumination with broad-spectrum light. As determined previously for cercosporin, superoxide production by illuminated altertoxins was increased by the addition of the reducing substances ergothioneine or urate; ascorbate also effectively increased superoxide production. Illuminated urate alone engendered some superoxide production.

Journal Article↗
PubMed1986

Mutagenicity of the Alternaria metabolites altertoxins I, II, and III.

The Ames Salmonella typhimurium assay was used to demonstrate that an extract of the mold Alternaria alternata was mutagenic. The mutagenic extract was fractionated, and the Ames test was used to determine which fractions were mutagenic. Subsequently, altertoxins I and II and a new compound referred to as altertoxin III were isolated by liquid chromatography and shown to be hydroxyperylenequinone compounds by mass spectrometry and infrared, ultraviolet, and proton magnetic resonance spectroscopy. Altertoxins I, II, and III were mutagenic to S. typhimurium TA98, TA100, and TA1537 with and without metabolic activation.

Alternaria↗
PubMed1980

Hepatocarcinogenicity of sterigmatocystin and versicolorin A to rainbow trout (Salmo gairdneri) embryos.

Versicolorin A (VA) and sterigmatocystin (ST) are biosynthetic precursors of aflatoxin B1 (AFB1). The carcinogenicity of these compounds relative to AFB1 was determined with the use of rainbow trout (Salmo gairdneri) embryo exposure. Exposure of 14-day rainbow trout embryos to a 0.5-ppm aqueous suspension of ST for 1 hour produced a 13% incidence of hepatocellular carcinomas among survivors 1 year later. Similar exposure of trout eggs to a 0.5-ppm solution of AFB1 produced a 53% incidence among survivors. Subsequent exposure of 21-day rainbow trout embryos to 5- and 25-ppm solutions of VA resulted in hepatocellular carcinoma incidences among survivors of 42 and 68%, respectively, at 12 months. A 0.5-ppm AFB1 positive control group had a 68% incidence among survivors of hepatocellular carcinomas at 1 year. These results established the carcinogenicity of VA for the first time and confirmed previous reports of ST carcinogenicity. Both compounds were of sufficient potencies to warrant caution as possible human health hazards.

Aflatoxins↗
PubMed1980

High pressure liquid chromatographic determination of satratoxins G and H in cereal grains.

A high pressure liquid chromatographic (HPLC) method is described for the detection and quantitative determination of satratoxins G and H in cereal grains. The toxins are extracted from the sample by blending with methanol--water (55 + 45) in the presence of hexane, followed by partitioning into chloroform. The chloroform extract is further purified on a 10 g silica gel column. A high pressure liquid chromatograph, equipped with a microparticle silica gel column and a 254 nm absorbance detector, is used for the determination. Additional confirmation of identity is obtained by mass spectrometry or by a brine shrimp bioassay of the HPLC eluates corresponding to the retention times of satratoxins G and H. The recoveries of added satratoxins G and H from wheat samples averaged 65% for G and 71% for H (200--1000 mg/kg). The coefficients of variation (CV) were 15% for G and 14% for H. The lower limit of detection was 200 microgram/kg for wheat. Analysis of corn, oats, and barley samples (400 microgram/kg of each toxin added) gave comparable recoveries. Only the corn extract exhibited HPLC interferences at the retention time for satratoxin H. The method was also used to analyze samples of corn, oats, wheat, barley, and rice on which Stachybotrys atra had been cultured.

Chromatography, High Pressure Liquid↗
PubMed1978

Production of xanthomegnin and viomellein by isolates of Aspergillus ochraceus, Penicillium cyclopium, and Penicillium viridicatum.

Fungal isolates from legumes were cultured on rice and examined for production of the toxic mold metabolites xanthomegnin and viomellein. Six of 14 Aspergillus ochraceus isolates produced from 0.3 to 1.3 mg of xanthomegnin per g and 0.1 to 1.0 mg of viomellein per g. One of nine isolates of Penicillium cyclopium produced 0.1 mg of xanthomegnin per g and 0.06 mg of viomellein per g. Three of nine P. viridicatum isolates produced from 0.4 to 1.6 mg of xanthomegnin per g and 0.2 to 0.4 mg of viomellein per g. This is the first report of xanthomegnin and viomellein production by A. ochraeus and P. cyclopium.

Aspergillus↗
PubMed1978

High pressure liquid chromatographic determination of xanthomegnin in corn.

A method is described for the detection and quantitative analysis of xanthomegnin in corn samples. Initial extraction with CHCl3 in the presence of 0.5M H3PO4 is followed by additional purification using silica gel column chromatography. A high pressure liquid chromatograph equipped with a microparticle silica gel column and a 405 nm absorbance detector is used for detection and quantitation of the xanthomegnin. The identity of xanthomegnin is confirmed by thin layer chromatography on silica gel plates developed with benzene-methanol-acetic acid (90 + 5 + 5). The recovery of xanthomegnin added to corn samples at levels of 0.75--9.6 mg/kg averaged 41% with a coefficient of variation of 25%.

Chromatography, High Pressure Liquid↗
PubMed1977

Isolation and identification of xanthomegnin, viomellein, rubrosulphin, and viopurpurin as metabolites of penicillium viridicatum.

Four of the metabolites of Penicillium viridicatum 66-68-2 grown on rice cultures were isolated and identified as xanthomegnin, viomellein, rubrosulphin, and viopurpurin. Melting points, elemental analysis, and infrared, ultraviolet, and field desorption and electron impact mass spectra of the isolated compounds were consistent with values reported in the literature for these compounds. In addition, diacetate and triacetate derivatives were prepared, and the chemical and physical analyses of the derivatives were also consistent with literature data. Proton magnetic resonance spectroscopy and thin-layer chromatography were also used for the additional identification of selected compounds.

Chemical Phenomena↗
PubMed1976

Determination of sterigmatocystin in corn and oats by gel permeation and high-pressure liquid chromatography.

Corn and oats samples are extracted with acetonitrile-water, followed by partition of the extract against hexane, transfer to chloroform, and elution from a silica gel column. The extract is purified by gel permeation chromatography on an automatic instrument. Reverse phase high-pressure liquid chromatography, using a 254 nm ultraviolet detector and 0.1 M KH2PO4-acetonitrile (7+5) as the mobile phase, is used for quantitation. The average recovery from 6 samples of corn to which 0, 25, 50, and 100 mug sterigmatocystin/kg had been added was 59%, with a coefficient of variation of 8.4%. The average recovery from oats fortified at the same levels was 74%, with a coefficient of variation of 12%. A confirmation procedure based on hemiacetal derivative formation on a thin layer chromatographic plate is also described.

Chromatography, Gel↗
PubMed1975

Collaborative study of a method for chemical confirmation of the identity of aflatoxin.

The chemical method for confirmation of the identity of aflatoxin by derivative formation directly on the TLC plate was studied collaboratively by 8 participants. The results show that aflatoxin B-1 was confirmed in 17 of 17 sample extracts representing 15 mu-g aflatoxin B-1/kg peanut butter, in 13 of 16 extracts representing 5 mu-g/kg, and in none of the 7 aflatoxin-free extracts. Collaborators commented that the method was easily performed and gave good results. The method has been adopted as official first action.

Aflatoxins↗