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At least 163 records · Page 9Linked to original sources
PubMed1987

Aflatoxins in sunflower seeds: effect of zinc in aflatoxin production by two strains of Aspergillus parasiticus.

Growth and aflatoxin production by Aspergillus parasiticus NRRL 2999 and Aspergillus parasiticus RC 12 were studied both in sunflower seed and a synthetic culture medium (with and without zinc enrichment). On a synthetic culture medium the strains behaved in different ways according to the zinc concentration. In sunflower seed medium the influence of zinc was not so evident. Thus the results show that the influence of zinc is not the same for different strains and substrates.

Aflatoxins↗
PubMed2005

Aflatoxin conducive and non-conducive growth conditions reveal new gene associations with aflatoxin production.

Research on aflatoxin (AF) production has traditionally focused on defining the AF biosynthetic pathway with the goal of identifying potential targets for intervention. To understand the effect of nitrogen source, carbon source, temperature, and pH on the regulation of AF biosynthesis, a targeted cDNA microarray consisting of genes associated with AF production over time was employed. Expression profiles for genes involved in AF biosynthesis grouped into five clades. A putative regulon was identified consisting of 20 genes that were induced in the conducive nitrogen and pH treatments and the non-conducive carbon and temperature treatments, as well as four other putative regulons corresponding to each of the four variables studied. Seventeen genes exhibited consistent induction/repression profiles across all the experiments. One of these genes was consistently downregulated with AF production. Overexpression of this gene resulted in repression of AF biosynthesis. The cellular function of this gene is currently unresolved.

Aflatoxins↗
PubMed1999

Quantitation and mapping of aflatoxin B1-induced DNA damage in genomic DNA using aflatoxin B1-8,9-epoxide and microsomal activation systems.

Aflatoxin B1 (AFB1) is a mutagenic and carcinogenic mycotoxin which may play a role in the etiology of human liver cancer. In vitro studies have shown that AFB1 adducts form primarily at the N7 position of guanine. Using quantitative PCR (QPCR) and ligation-mediated PCR (LMPCR), we have mapped total AFB1 adducts in genomic DNA treated with AFB1-8,9-epoxide and in hepatocytes exposed to AFB1 activated by rat liver microsomes or human liver and enterocyte microsomal preparations. The p53 gene-specific adduct frequencies in DNA, modified in cells with 40-400 microM AFB1, were 0.07-0.74 adducts per kilobase (kb). In vitro modification with 0. 1-4 ng AFB1-8,9-epoxide per microgram DNA produced 0.03-0.58 lesions per kb. The adduct patterns obtained with the epoxide and the different microsomal systems were virtually identical indicating that adducts form with a similar sequence-specificity in vitro and in vivo. The lesions were detected exclusively at guanines with a preference towards GpG and methylated CpG sequences. The methods utilizing QPCR and LMPCR thus provide means to assess gene-specific and sequence-specific AFB1 damage. The results also prove that microsomally-mediated damage is a suitable method for avoiding manipulations with very unstable DNA-reactive metabolites and that this damage can be detected by QPCR and LMPCR.

Aflatoxin B1↗
PubMed2001

Differential effects of acetaminophen pretreatment on hepatic aflatoxin B(1)-DNA binding, cellular proliferation, and aflatoxin B1-induced hepatic foci in rats and hamsters.

Effects of acetaminophen (AAP) pretreatment on hepatic aflatoxin B1 (AFB(1))-DNA binding, cellular proliferation, and AFB(1)-induced glutathione S-transferase placental form (GST-P) positive hepatocytes and foci have been examined in young male rats and hamsters. Intraperitoneal (i.p.) dosing of 600mg AAP 3h before AFB(1) i.p. injection showed three-fold more AFB(1)-DNA binding in hamsters and 40% less binding in rats. Cell proliferation analyzed by bromodeoxyuridine incorporation was not significant (0.4-0.6%) 24-96h after AAP (600mg) treatment of rats; however, proliferation was stimulated and was maximum (11%) in hamsters at 72h after AAP treatment. Dosing of rats with AFB(1) alone at 0.5 or 2.5mg level gave an appreciable number of GST-P positive minifoci (two to nine cells) with a few foci larger than 100 microm; pretreatment with AAP (300 or 600mg) 48h before 0.5 or 2.5mg AFB(1) had no effect on the number and focal area of foci. In hamsters, 1 or 2mg AFB(1) alone yielded GST-P positive hepatocytes without any minifoci. Pretreatment with AAP (600mg) 48 or 72h before 1 or 2mg AFB(1) produced increases in both GST-P positive hepatocytes and minifoci. Thus, marked changes are observed after AAP pretreatment in hamsters compared to rats.

Acetaminophen↗
PubMed2006

Unraveling the aflatoxin-FAPY conundrum: structural basis for differential replicative processing of isomeric forms of the formamidopyrimidine-type DNA adduct of aflatoxin B1.

Aflatoxin B1 (AFB) epoxide forms an unstable N7 guanine adduct in DNA. The adduct undergoes base-catalyzed ring opening to give a highly persistent formamidopyrimidine (FAPY) adduct which exists as a mixture of forms. Acid hydrolysis of the FAPY adduct gives the FAPY base which exists in two separable but interconvertible forms that have been assigned by various workers as functional, positional, or conformational isomers. Recently, this structural question became important when one of the two major FAPY species in DNA was found to be potently mutagenic and the other a block to replication [Smela, M. E.; Hamm, M. L.; Henderson, P. T.; Harris, C. M.; Harris, T. M.; Essigmann, J. M. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 6655-6660]. NMR studies carried out on the AFB-FAPY bases and deoxynucleoside 3',5'-dibutyrates now establish that the separable FAPY bases and nucleosides are diastereomeric N5 formyl derivatives involving axial asymmetry around the congested pyrimidine C5-N5 bond. Anomerization of the protected beta-deoxyriboside was not observed, but in the absence of acyl protection, both anomerization and furanosyl --> pyranosyl ring expansion occurred. In oligodeoxynucleotides, two equilibrating FAPY species, separable by HPLC, are assigned as anomers. The form normally present in duplex DNA is the mutagenic species. It has previously been assigned as the beta anomer by NMR (Mao, H.; Deng, Z. W.; Wang, F.; Harris, T. M.; Stone, M. P. Biochemistry 1998, 37, 4374-4387). In single-stranded environments the dominant species is the beta anomer; it is a block to replication.

Aflatoxin B1↗
PubMed2002

Aflatoxin binders I: in vitro binding assay for aflatoxin B1 by several potential sequestering agents.

Nine potential proprietary sequestering agents consisting of 4 activated charcoals, 3 sodium bentonites, a calcium bentonite, and an esterified glucomannan were compared in a novel in vitro assay for aflatoxin B1 (AFB1) binding. Agents were evaluated in 10% methanol prepared as 1% stirred suspensions at pH 3, 7, 10 and pH-unadjusted, with or without AFB1 at 5 microg/ml. All nine agents bound more than 95% of the 5 microg of AFB1 in solution, regardless of pH. The sodium bentonites bound 98, 95, and 98% of the AFB1. The four activated charcoals bound over 99%, the calcium bentonite bound 98%, and the esterified glucomannan bound 97% of the AFB1 in solution. The results suggested that the sequestering agents tested here had sufficient potential to bind AFB1 at pH values commonly found in the gastrointestinal tracts of ruminants and other animals.

Aflatoxin B1↗
PubMed2004

Effect of diet on aflatoxin B1-DNA binding and aflatoxin B1-induced glutathione S-transferase placental form positive hepatic foci in the rat.

Effects of diets on hepatic aflatoxin B1 (AFB1)- DNA binding and AFB1-induced glutathione S- transferase placental (GST-P) form positive hepatic foci have been examined in young male Fischer rats. Animals were fed either AIN-76A or Purina Chow (PC) diet for 1 wk before AFB1- DNA binding studies in vivo and in vitro. Animals were injected i.p. with AFB1 (1 mug/kg body wt) and 3 days later were given either AIN-76A or PC diet with or without 0.1% phenobarbital (PB) in their drinking water. All animals were sacrificed 10 wks after AFB1 dosing for analysis of AFB1-induced GST-P positive hepatic foci by immunochemistry. Two h after i.p. injection of AFB1, hepatic AFB1-DNA binding in AIN-76A fed rats was twice as much as those in PC fed animals without affecting GSH levels. There was no significant effect of diet on either cytochrome P-450 content, GSH levels or microsomal cytochrome P-450 mediated AFB1-DNA binding to exogenous DNA. There was a 40% increase in cytosolic GSH S-transferase activity with 1-chloro-2,4-dinitrobenzene as a substrate in PC fed animals compared to those given AIN- 76A diet. The number and area of AFB1-induced GST-P positive hepatic foci were twice and fivefold as much in AIN-76A fed compared to those in PC fed rats. The number of AFB1-induced GST-P positive foci was increased 5-10 fold in the presence of PB in both groups. In summary, the present data indicate that feeding of PC diet compared to AIN-76A diet inhibits the initiation phase whereas AIN-76A stimulates the promotion phase of AFB1 hepatocarcinogenesis in rats by inhibiting AFB1-DNA binding and increasing AFB1-induced hepatic foci respectively.

Aflatoxin B1↗
PubMed2006

Effect of water molecules on the fluorescence enhancement of Aflatoxin B1 mediated by Aflatoxin B1:beta-cyclodextrin complexes. A theoretical study.

In order to explain the observed fluorescence enhancement of Aflatoxin B1 (AFB1) when forming AFB1:beta-cyclodextrin (AFB1:beta-CD) inclusion complexes, we have performed a theoretical (quantum chemistry calculations) study of AFB1 and AFB1:beta-CD in vacuum and in the presence of aqueous solvent. The AM1 method was used to calculate the absorption and emission wavelengths of these molecules. With the help of density functional theory (DFT) and time-dependent DFT (TDDFT) vibrational frequencies and related excitation energies of AFB1 and AFB1.(H2O)m = 4,5,6,11 were calculated. On the basis of these calculations we propose a plausible mechanism for the fluorescence enhancement of AFB1 in the presence of beta-CD: (1) before photoexcitation of AFB1 to its S1 excited state, there is a vibrational coupling between the vibrational modes involving the AFB1 carbonyl groups and the bending modes of the nearby water molecules (CG + WM); (2) these interactions allow a thermal relaxation of the excited AFB1 molecules that results in fluorescence quenching; (3) when the AFB1 molecules form inclusion complexes with beta-CD the CG + WM interaction decreases; and (4) this gives rise to a fluorescence enhancement.

Aflatoxin B1↗
PubMed1991

Ethoxyquin-induced resistance to aflatoxin B1 in the rat is associated with the expression of a novel alpha-class glutathione S-transferase subunit, Yc2, which possesses high catalytic activity for aflatoxin B1-8,9-epoxide.

A purification scheme has been devised for two ethoxyquin-inducible Alpha-class glutathione S-transferases (GSTs) which possess at least 25-fold greater activity towards aflatoxin B1 (AFB1)-8,9-epoxide than that exhibited by the GSTs (i.e. F, L, B and AA) that have been described previously. These two enzymes are both heterodimers and both contain a subunit of Mr 25,800. This subunit has been isolated from both of the GST isoenzymes and, after cleavage with CNBr, it has been subjected to automated amino acid sequencing. The primary structure of the Mr 25,800 subunit revealed that it forms part of a subfamily of Alpha-class GSTs which possess closest identity (about 92%) with the Yc subunit of apparent Mr 27,500, which is encoded by the recombinant cDNA clone pGTB42 [Telakowski-Hopkins, Rodkey, Bennett, Lu & Pickett (1985) J. Biol. Chem. 260, 5820-5825]. As these two GSTs possess less than 70% sequence identity with the Ya1 and Ya2 subunits, both of Mr 25,500, the constitutively expressed Yc subunit of Mr 27,500 has been renamed Yc1 and the ethoxyquin-inducible GST of Mr 25,800 has been designated Yc2. Using this nomenclature, the two GSTs with high activity for AFB1-8,9-epoxide are Ya1Yc2 and Yc1Yc2. Although evidence suggests that induction of Yc2 is responsible for the high detoxification capacity of livers from ethoxyquin-treated rats for AFB1-8,9-epoxide, resistance towards AFB1 may be multifactorial in this instance as dietary ethoxyquin also induces the Ya1, Ya2 and Yc1 subunits about 2.2-, 10.9- and 2.7-fold respectively. Besides the induction of GST by ethoxyquin, activity towards AFB1-8,9-epoxide is also elevated in the livers of neonatal rats and in livers that contain preneoplastic nodules. Western blotting experiments show that Yc2 is not present in hepatic cytosol from adult rats fed on normal diets but is expressed in neonatal rat livers and in the livers of adult rats that contain preneoplastic nodules that have arisen as a consequence of consuming diets contaminated with AFB1.

Aflatoxin B1↗
PubMed1991

Aflatoxin production via cross-feeding of pathway intermediates during cofermentation of aflatoxin pathway-blocked Aspergillus parasiticus mutants.

Cofermentation of Aspergillus parasiticus strains (SRRC 163 and SRRC 2043) blocked at different steps in the aflatoxin B1 (AFB1) biosynthetic pathway in a synthetic liquid medium or on seeds (cottonseed, corn kernels, and peanuts) resulted in production of AFB1. Strain SRRC 2043 accumulated O-methylsterigmatocystin (OMST), a late precursor in AFB1 biosynthesis, whereas SRRC 163 accumulated averantin, an early precursor in the pathway. Strain SRRC 2043 secreted large amounts of OMST in culture relative to the amounts of several other pathway intermediates secreted into media (by other AFB1 pathway-blocked strains). AFB1 production occurred even when colonies of SRRC 163 and SRRC 2043 strains (producing no detectable AFB1) were grown together on an agar medium while physically separated from each other by a filter membrane (0.22-micron pore size). In addition, when mycelia of strain SRRC 163 were added to culture filtrates (containing no mycelia but containing secreted OMST) of strain SRRC 2043, AFB1 production occurred. The results suggested a chemical (rather than genetic) mechanism of complementation for AFB1 production between AFB1 pathway-blocked strains, since no mycelial contact was required between these strains for AFB1 production. The mechanism for chemical complementation involves secretion of OMST by SRRC 2043 and subsequent absorption and conversion of OMST to AFB1 by mycelia of strain SRRC 163.

Aflatoxin B1↗
PubMed1991

Alteration of aflatoxin B1 metabolic profiles and reduction of aflatoxin B1 mutagenicity by hepatic microsomes of rats fed butylated hydroxyanisole.

Effect of administering butylated hydroxyanisole (BHA) on the metabolism of aflatoxin B1 (AFB1) and production of mutagenic metabolites have been compared with those of phenobarbital (PB) and 3-methylcholanthrene (MC) administration in rat liver microsomes. Male Sprague-Dawley rats were treated with these inducers and liver microsomes were isolated. These microsomes were used to metabolize AFB1 and to produce mutagenic metabolites. Results showed that normal rat liver were able to metabolize AFB1 quite actively and produced large amounts of AFB-8,9-epoxide (appearing as the AFB-8,9-dihydrodiol-Tris complex). Upon incubations of normal rat liver microsomes with increasing concentrations of AFB1, a steep dose-related increases of mutagenicity was observed in the Ames test. The PB-microsomes had an increased ability to metabolize AFB1 and particularly the rate for the production of the weakly mutagenic AFQ1 metabolite was markedly increased. Conversely, PB-microsomes had a moderate decrease in its ability to form the strongly mutagenic of AFB-8,9-epoxide metabolite. However, the ability of PB-microsomes to form mutagenic metabolites from AFB1 was somewhat greater than that of the control-microsomes. The MC-microsomes had an increased ability to metabolize AFB1 also. However, instead of the weakly mutagenic AFQ1 metabolite seen with the PB-microsomes, large amounts of the strongly mutagenic AFM1 metabolite was formed. Although AFM1 is not known to be a direct mutagen, it was highly mutagenic upon activation with microsomes. The very steep dose-related increases of mutagenicity and appearance of bacterial toxicity at relatively lower doses of AFB1 may have been caused by the secondary metabolic activation. The ability of BHA-microsomes to metabolize AFB1 was decreased. Among the metabolites produced by the BHA-microsomes, the non-mutagenic AFB2a was formed in significantly increased amounts but the toxic AFB-8,9-epoxide was produced only in much reduced amounts. The AFB2a was not mutagenic even after metabolic activation with microsomes. When increasing concentrations of AFB1 was incubated with BHA-microsomes, a very mild dose-related increases of mutagenicity was observed and the occurence of toxic effects on bacterial growth appeared only at high doses of AFB1. This may have been due both to the reduced rate of overall AFB1 metabolism and to the decreased formation of the highly mutagenic AFB-8,9-epoxide but an increased formation of the non-mutagenic AFB2a metabolite by the BHA-microsomes.(ABSTRACT TRUNCATED AT 400 WORDS)

Aflatoxin B1↗
PubMed2003

Reduction of aflatoxins by Korean soybean paste and its effect on cytotoxicity and reproductive toxicity--part 2. Antigenotoxic effects of the methanol extract of Korean soybean paste (doen-jang) on aflatoxin B1-induced bacterial reverse mutation and chromosome aberration.

A bacterial reverse-mutation assay with Salmonella Typhimurium TA1535, TA1537, TA98, TA100, and TA102 and an in vitro chromosome aberration assay with Chinese hamster lung (CHL) cells were used to investigate the genotoxicity of the methanol extract of Korean soybean paste (doen-jang [dwen-jahng]) and its antigenotoxic activity against aflatoxin B1. The methanol extract revealed nonmutagenic potential for all of the bacterial strains tested. The extract significantly reduced the numbers of revertants per plate when it was added to the assay system with Salmonella Typhimurium TA100 (P < 0.05). The extract also exhibited significant inhibitory effects on chromosome aberration in CHL cells (P < 0.05). The findings of this work indicate that the methanol extract of Korean soybean paste could have strong potential as an antigenotoxic material.

Aflatoxin B1↗
PubMedDate not supplied

Indole-3-carbinol induces a rat liver glutathione transferase subunit (Yc2) with high activity toward aflatoxin B1 exo-epoxide. Association with reduced levels of hepatic aflatoxin-DNA adducts in vivo.

Aflatoxin B1 (AFB1), a metabolite of the grain mold Aspergillus flavus, is a potent hepatocarcinogen and widespread contaminant of human food supplies. AFB1-induced tumors or preneoplastic lesions in experimental animals can be inhibited by cotreatment with several compounds, including indole-3-carbinol (I3C), a component of cruciferous vegetables, and the well-known Ah receptor agonist beta-naphthoflavone (BNF). This study examines the influence of these two agents on the AFB1-glutathione detoxication pathway and AFB1-DNA adduction in rat liver. After 7 days of feeding approximately equally inhibitory doses of I3C (0.2%) or BNF (0.04%) alone or in combination, male Fischer 344 rats were administered [3H]AFB1 (0.5 mg/kg, 480 microCi/kg) intraperitoneally and killed 2 hr later. All three experimental diets inhibited in vivo AFB1-DNA adduction (BNF, 46%; I3C, 68%; combined, 51%). Based on Western blots using antibodies specific for the glutathione S-transferase (GST), subunit Yc2 (subunit 10) appeared to be substantially elevated by the diets containing I3C (I3C diet, 4.0-fold increase in band density; combined diet, 2.8-fold). The BNF diet appeared to elevate Yc2 to a lesser extent (2.2-fold increase in band density).(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxin B1↗
PubMed1998

Detectable levels of serum aflatoxin B1-albumin adducts in the United Kingdom population: implications for aflatoxin-B1 exposure in the United Kingdom.

This study aimed to estimate aflatoxin B1 (AFB1) exposure in the United Kingdom population by measuring levels of serum AFB1-albumin (alb), using immunoassay and high-performance liquid chromatography (HPLC) with fluorescence detection. A self-questionnaire on dietary habits from 104 volunteers (47 men and 57 women) in York was completed, and blood samples were collected. Serum alb was extracted, and AFB1-lysine (lys), the digest product of AFB1-alb, was isolated and measured. A sensitive ELISA (detection limit, approximately 1.4 pg of AFB1-lys) was developed. A good correlation was found between calibration of ELISA results and scintillation counting, for rats dosed with [3H]AFB1 (r = 0.972; P < 0.001). This ELISA was subsequently used to analyze human serum alb. For United Kingdom human sera, the mean adduct levels were 29.3 +/- 14.8 pg AFB1-lys equivalents (eq) mg albumin (males) and 26.9 +/- 14.4 pg AFB1-lys eq/mg alb (females). Confirmation of the ELISA data was sought using reversed-phase HPLC with fluorescence detection. HPLC chromatograms of digested York serum alb were compared to digested serum alb for humans from Qidong County, People's Republic of China, and from AFB1-dosed rats. These all gave similar HPLC profiles. Each sample contained fluorescent material that coeluted with and just before the AFB1-lys standard. Fluorescent fractions were found to be inhibitory in a separate anti-AFB1-lys ELISA, indicating that these earlier fluorescent peaks contained AFB1 residues. Our results suggest that measurable internal AFB1 exposure may be occurring in some United Kingdom individuals, albeit at lower levels than those seen for areas with high AFB1 exposure. The source of this exposure may reflect the known difficulties in accurately monitoring regulated imported foodstuffs and/or the lack of regulations on other potentially contaminated imports. However, no positive correlations were found between our AFB1-lys measurements and any dietary questionnaire information. Animal studies, as well as human studies, have been important in developing exposure and internal adduct relationships in humans. Based on this literature, our AFB1-alb data indicate a mean daily exposure of 3 microg of AFB1 and a mean internal dose in liver DNA of 5.9 adducts/10(7) nucleotides. We believe this may be an overestimate of the AFB1 exposure level in the United Kingdom, and further studies are needed to accurately relate external dose and internal AFB1 biomarkers in humans.

Adolescent↗
PubMed1976

Metabolism of aflatoxin B1 to aflatoxins Q1, M1 and P1 by mouse and rat.

We have used a microtechnique to study (a) the metabolism of aflatoxin (AF)B1 by rat and mouse, and (b) the effect of phenobarbital treatment in vivo on the in vitro metabolism of AFB1 by hepatic microsomes from rat and mouse. The results indicate and AFP1, the O-demethylated product of AFB1, is a major metabolite produced by the mouse. Although it is detectable in rat, the amount produced is negligible and was calculated to be at least 10 times less than that produced by the mouse. Using several microincubations, AFP1 was prepared in sufficient quantities to verify its identity by UV spectroscopy and by thin layer chromatography against an authentic standard in six different solvent systems. Phenobarbital pretreatment resulted in an enhancement in the total metabolism of AFB1 as well as in the formation of AFM1, AFQ1 and AFP1.

Aflatoxins↗