• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2565-2570
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• 2014

H19 is an imprinted oncofetal gene, and loss of imprinting at the H19 locus results in over-expression of H19 in cancers. Aflatoxin B1(AFB1) is regarded as one of the most dangerous carcinogens. Exposure to AFB1 would most easily increase susceptibility to diseases such as hepatocellular carcinoma(HCC) but any possible relationship between AFB1 and H19 is not clear. In present study, we found that AFB1 could up-regulate the expression of H19 and promote cell growth and invasion by hepatocellular carcinoma HepG2 cells. Knocking down H19 RNA co ld reverse the effects of AFB1 on cell growth and invasion. In addition, AFB1 induced the expression of E2F1 and its knock-down could down-regulate H19 expression and suppress cell growth and invasion in hepatocellular carcinoma HepG2 cells. Furthermore, E2F1 over-expression could up-regulate H19 expression and promote cell growth and invasion, with binding to the H19 promoter being demonstrated by chromatin immunoprecipitation assays (ChIP). In summary, our results suggested that aflatoxin B1could promote cell growth and invasion in hepatocellular carcinoma HepG2 cells through actions on H19 and E2F1.

• Journal of Microbiology and Biotechnology
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• v.27 no.1
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• pp.57-66
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• 2017

Aflatoxins are classified as Group 1 (carcinogenic to humans) by the International Agency for Research on Cancer. In this study, a total of 134 fungal strains were isolated from 65 meju samples, and two fungal isolates were selected as potential aflatoxin $B_1$ ($AFB_1$)-biodetoxification fungi. These fungi were identified as Aspergillus oryzae MAO103 and A. oryzae MAO104 by sequencing the beta-tubulin gene. The two A. oryzae strains were able to degrade more than 90% of $AFB_1$ (initial concentration: $40{\mu}g/l$) in a culture broth in 14 days. The mutagenic effects of $AFB_1$ treated with A. oryzae MAO103 and MAO104 significantly decreased to 5.7% and 6.4%, respectively, in the frame-shift mutation of Ames tests using Salmonella typhimurium TA98. The base-substituting mutagenicity of $AFB_1$ was also decreased by the two fungi. Moreover, $AFB_1$ production by Aspergillus flavus was significantly decreased by the two A. oryzae strains on soybean-based agar plates. Our data suggest that the two $AFB_1$-detoxifying A. oryzae strains have potential application to control $AFB_1$ in foods and feeds.

• Applied Microscopy
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• v.21 no.1
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• pp.63-76
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• 1991

Butylated hrdroxyanisole(BHA), a widely used food additive phenolic antioxidant, is known to inhibit cancer formations inducible with a wide variety of chemical carcinogens including aflatoxin $B_1(AFB_1)$. Thus, in the present study morphological characteristics underlying the hepatoprotective effects of BHA against $AFB_1$ inducible ultrastructural changes of hepatocytes have been examined. The obtained results are as follows : 1 . Livers obtained from rats treated with $AFB_1$ in vivo have been examined with transmission electron microscope. Among the many hepatocellular structural aberrations induced by $AFB_1$ treatment, the nuclear chromatins were found to be distributed irregularly('cap formation') and the nuclear membrane was found to be partially segregated. Furthermore, there were many lipid droplets, hyperplasia of smooth endoplasmic reticulum, dialated rough endoplasmic reticulum and, lysosomes arrested at various stages of its development. 2. Also, when $AFB_1$ was given in vitro to hepatocytes which have been isolated from untreated normal rats and examined under scanning electron microscope, there were much 'blobbing' phenomena resulting from cytoskeletal disturbances. 3. However, in the liver obtained from rats pretreated with BHA and then give the $AFB_1$, the observed morphological aberrations were in much reduced extent. Similarly, the BHA-hepatocytes had much decreased severity in the $AFB_1$ inducible blob formations.

• Journal of Ginseng Research
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• v.35 no.2
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• pp.243-249
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• 2011

Korean red ginseng (KRG), the steamed root of Panax ginseng Meyer, has a variety of biological properties, including anti-inflammatory, antioxidant and anticancer effects. Aflatoxin $B_1$ ($AFB_1$) produced by the Aspergillus spp. causes acute hepatotoxicity by lipid peroxidation and oxidative DNA damage, and induces liver carcinoma in humans and laboratory animals. This study was performed to examine the protective effects of KRG against hepatotoxicity induced by $AFB_1$ using liver-specific serum marker analysis, histopathology, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. In addition, to elucidate the possible mechanism of hepatoprotective effects, superoxide dismutase, catalase, glutathione peroxidase, and malondialdehyde were analyzed. Rats were treated with 250 mg/kg of KRG (KRG group) or saline ($AFB_1$ group) for 4 weeks and then received 150 ${\mu}g/kg$ of $AFB_1$ intraperitoneally for 3 days. Rats were sacrificed at 12 h, 24 h, 48 h, 72 h, or 1 wk after $AFB_1$ treatment. In the KRG pre-treatment group, serum alanine aminotransferase, aspartate aminotransferase, and malondialdehyde levels were low, but superoxide dismutase, catalase, and glutathione peroxidase activities were high as compared to the $AFB_1$ alone group. Histopathologically, $AFB_1$ treatment induced necrosis and apoptosis in hepatocytes, and led to inflammatory cells infiltration in the liver. KRG pre-treatment ameliorated these changes. These results indicate that KRG may have protective effects against hepatotoxicity induced by $AFB_1$ that involve the antioxidant properties of KRG.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.11
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• pp.1639-1645
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• 2002

The purpose of this study was to investigate the effects of aflatoxin $B_1$ ($AFB_1$) on the ultracellular morphology alteration, apoptosis induction and reactive nitrogen and oxygen intermediates production of peritoneal macrophages (DPM) from mule ducks. The ducklings were purchased from a commercial hatchery, and were fed a corn-soybean based diet. As the ducklings were grown up to 3 wk of age, the Sephadex-elicited peritoneal exudative cells (PEC) were used as the source for duck peritoneal macrophages. The ultracellular morphology study showed that significant number of cells shifted from category I (normal cell with ruffled membrane) and II (cell membrane blebbing) to category III (cell membrane blebbing and even rupture) after DPM were incubated with $AFB_1$ ($20{\mu}g/ml$) for 12 to 48 h. When DPM were exposed to $AFB_1$ in vitro, the production of NO, $H_2O_2$ and $O_2{^-}$ in macrophages was reduced after 12-48 h incubation with previous LPS stimulation. There was a DNA laddering pattern observed in DPM incubated with $AFB_1$ 5, 10, 20, 50 or $100{\mu}g/ml$ for 12 h. Evidence also revealed that the percentage of apoptotic cells was increased along with the elevation of $AFB_1$ concentration. The results suggest that $AFB_1$ exposure causes duck macrophages going on apoptotic pathway through evidence of ultracellular morphology alteration and DNA laddering in agarose electrophoresis. The production of reactive nitrogen and oxygen intermediates of duck macrophages also depressed after $AFB_1$ exposure, and this implied that $AFB_1$ could cause deteriorated functions of bacteriocidal and tumoricidal activity in duck macrophages.

• Toxicological Research
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• v.34 no.3
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• pp.211-220
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• 2018

Early life exposure to aflatoxin B1 (AFB1) and low protein diet through complementary foods during weaning is common in parts of Africa and Asia. This study evaluated the effect of co-exposure to AFB1 and low protein diet on the extrahepatic tissues of rats. Twenty-four three-week old weanling male albino rats were used for this study and were randomly assigned into four groups: group 1 served as control and was fed normal protein diet (20% protein), group 2 was fed low protein diet (5% protein), group 3 was fed normal protein diet + 40 ppb AFB1 while group 4 received low protein diet + 40 ppb AFB1, all for eight weeks. Afterward, biomarkers of anemia (packed cell volume (PCV), hemoglobin) and kidney function (urea, uric acid, and creatinine) were determined in the blood while biomarkers of oxidative stress were determined in the tissues spectrophotometrically. Co-exposure to AFB1 and low protein diet significantly (p < 0.05) decreased body weight gain and PCV, increased biomarkers of kidney functions and induced oxidative stress in the tissues studied. There was significant (p < 0.05) reduction in glutathione concentration while TBARS was significantly increased in the tissues. Co-exposure to AFB1 and low protein diet had additive effects on decreasing the weight gain and potentiation effect of kidney dysfunction in the rats. The co-exposure also decreased antioxidant enzymes and increased oxidant status in the tissues. Our results demonstrate that this co-exposure has deleterious health effects on extrahepatic tissues and should be a public health concern especially in developing countries where AFB1 contamination is common.

• Food Science and Biotechnology
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• v.14 no.6
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• pp.866-870
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• 2005

The 14 lactic acid bacteria (LAB) have been evaluated to determine the binding capacity to HT29 cell and Aflatoxin $B_1$ ($AFB_1$). The interaction of LAB to HT29 cells has been further investigated to identify the possibility of competing the binding sites with $AFB_1$. Of 14 LAB strains, Lactobacillus casei KCTC 3260 demonstrated the higher adhesiveness to HT29 and $AFB_1$ with the rate of 19.6% and 46.3%, respectively. In competitive analysis for binding sites, the adhesion of L. casei KCTC 3260 to HT29 cells was reduced with 100 nmol $AFB_1$ by 31.2%. The protoplast of L. casei KCTC 3260 showed no binding capacity to HT29 cells with increment of $AFB_1$ concentration, indicating that cell wall components might serve as a critical factor for the binding. To discriminate the major component influencing on L. casei KCTC 3260 binding to HT29 cells and $AFB_1$, four different pre-treatments (lipase, pronase E, sodium m-periodate, and urea) were employed. Of those, sodium m-periodate treatment caused the lower adhesion of L. casei KCTC 3260 to HT29 cells with the increment of $AFB_1$ concentration. These results indicated that carbohydrate moiety on the cell wall of L. casei KCTC 3260 might be the most critical component in binding to both HT29 cells and $AFB_1$.

• Journal of Microbiology and Biotechnology
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• v.16 no.4
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• pp.643-646
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• 2006

Because of potential health hazards of aflatoxins for humans, the present study was conducted to monitor aflatoxin $B_1\;(AFB_1)$ in livestock feeds. A total of 249 samples of feeds collected in Korea were analyzed by DC-ELISA for qualitative analysis of $AFB_1$. Then, 27 samples that were verified to contain $AFB_1$ by DC-ELISA were quantitated by HPLC/FLD. HPLC/FLD analysis revealed that only one sample collected from a farm contained 11 ppb of $AFB_1$, whereas the other samples collected from feed companies did not contain $AFB_1$. The presence of $AFB_1$ was further confirmed by LC/MS analysis. TLC analysis indicated that the result of the DC-ELISA was most likely due to possible contamination of other mycotoxins rather than $AFB_1$. In conclusion, HPLC/FLD analysis following DC-ELISA is necessary for rapid and accurate detection of $AFB_1$.

• Journal of Food Hygiene and Safety
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• v.33 no.6
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• pp.453-459
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• 2018

This study was performed to investigate the contamination levels of heavy metals (such as lead, cadmium, arsenic and mercury) and aflatoxin (such as $B_1$, $B_2$, $G_1$ and $G_2$) in commercial herbs for food and medicine. The concentrations of the heavy metals were measured by the ICP-MS and a mercury analyzer. The aflatoxins were analyzed by a HPLC-florescence coupled with photochemical derivatization. The detection ranges of the lead, cadmium, arsenic and mercury were found to be 0.006~4.088 mg/kg, 0.002~2.150 mg/kg, ND~0.610 mg/kg and ND~0.0139 mg/kg respectively. Among the total samples, the 3 samples (2.6%) were not suitable for the specification of cadmium by the MFDS (Ministry of Food and Drug Safety). The 13 samples of the total 117 samples were aflatoxin positive (11.1%). The amount of aflatoxin $G_1$ was $0.7834{\mu}g/kg$ in the Puerariae Radix and aflatoxin $G_2$ were $0.3517{\mu}g/kg$, $0.4881{\mu}g/kg$ in two samples of the Glycyrrhizae Radix et Rhizoma, respectively. The aflatoxins $B_2$ and $G_1$ were simultaneously detected in the 10 Angelicae Gigantis Radix. The detection ranges of aflatoxins $B_2$ and $G_1$ were $0.2324{\sim}1.0358{\mu}g/kg$ and $0.7552{\sim}1.6545{\mu}g/kg$ respectively in Angelicae Gigantis Radix. The results of the current study suggest that continuous monitoring is needed for the proactive management of commercial herbs for food and medicine safety.

• Parasites, Hosts and Diseases
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• v.25 no.2
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• pp.99-109
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• 1987

The present study was carried out to examine the effect of a calcinogen, aflatoxin B1 on the ultrastructural changes of ciliary epithelial cells in mice infected with Clonerchis sinensis. A total of 93 male albino mice(BALB/c strain) was divided into 3 groups; group I, treated with 1.0 ppm aflatoxin Bl for 12 weeks; group II, given 50 C. sinensis n;etacercariae, and group III, given 50 metacercariae and treated with 1.0 ppm aflatoxin Bl for 12 weeks. Three mice served for untreated-uninfected controls. From 4 weeks after the treatsment and/or in(ection, three mice from each group were sacrificed at 4 week intervals up to the 40th week, and their hepatobiliary tissues were prepared for transmission electron microscopy. The most prominent ultrastructural changes in group I were remarkable enlargement of nuclear size, separation of nucleolus, dispersed chromatin granules in nuclei and increased dense granules along the inner membrane of nuclei. In the cytoplasm there was slight proliferation of mitochondria and endoplasmic reticulum (ER) at earlier stage. At the 12th week separation of fibrillar and granular components of the nucleolus was a characteristic finding. As the time elapsed, epithelial cells showed fiattened-cuboidal form and a tendency of atrophy. Most of the nuclei were elongated and polygonal in shape. In group II the appearance of elaborate interwoven folds of lateral cytoplasm forming a labyrinth of interconnected intercellular space and variety in nuclear shape were the prominent fadings at earlier stage. The cytoplasm showed slight proliferation and dilatation of mitochondria and ER, and a small number of mucin droplets. In the basement membrane scanty fibrous cells were seen. With time, variety in nuclear shape, marked proliferation and dilatation of rough ER and some collagen fibrils were demonstrated. Other features of intracellular organelles and mucin droplets persisted. In group III cuboidal epithelial cells showed their remarkably enlarged and irregular nuclei, increased chromatin granules in the nuclei, separated nucleoli, proliferated and dilated rough ER. With time, sequestered mitochondria showed blob-like evaginations which lacked cristae and dense matrix, and were limited by a single membrane. Since the 20th week, microvilli were relatively scanty and poorly developed. Organelles and inclusions in the cytoplasm of metaplastic cells were poor. Nuclei were variable in shape. The nlost prominent changes at later stage were separation of nuclei from the cytoplasm, and appearance of numerous and irregularly angled electron dense granules in the nuclei.