• 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.

• Korean Journal of Poultry Science
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• v.44 no.4
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• pp.283-290
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• 2017

Totally, one hundred and sixty 1-day-old Ross 308 broiler chicks were fed with a diet containing 0, 0.5, 1.0, and 2.0 mg of aflatoxin $B_1(AFB_1)/kg$ of feed for 21 days. Body weight was lower for the $AFB_1$-treated broilers than for the control group. At 14 and 21 DPF, the broilers fed with 2.0 mg of $AFB_1/kg$ of feed weighed significantly lower than those of the other groups (p<0.05). Relative liver weights increased significantly in a dose-dependent manner, and relative spleen weights were significantly high in the chicks fed with 2.0 mg of $AFB_1/kg$ of feed at 21 DPF (p<0.001). Biochemical analyses showed that total protein and albumin levels decreased significantly at 7 and 14 DPF for the chicks of the group fed with 2.0 of mg $AFB_1/kg$ of feed, compared with those fed with 0.5 and 1.0 mg of $AFB_1/kg$ of feed (p<0.05). AST and ALT levels increased significantly at 14 and 21 DPF (p<0.05), and the AST levels, particularly, increased dose-dependently (p<0.05). Histopathological analyses showed that the liver tissues of the $AFB_1$-treated chicks showed significant lesions, including hemorrhage, hepatocyte necrosis, inflammatory cell infiltration, and fatty degeneration. The severity of both hepatocyte necrosis and inflammatory cell infiltration appeared to increase dose- and time-dependently. Similarly, hepatic fibrosis increased dose-dependently (p<0.05). The results of this study could improve our understanding of parameters used for evaluating aflatoxicosis in poultry.

• 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.

• 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.

• The Korean Journal of Food And Nutrition
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• v.16 no.4
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• pp.303-309
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• 2003

This study was performed to investigate the antimutagenic and antioxidative activities of pine pollen with respect to the microbial mutation induced by various mutagens such as 1-NP, daunomycin, 2-NF, MNNG, NaN$_3$, 4NQO, 4-NOPD, AFB$_1$, Trp-P-1, 2-AF and oxidative mutagens such as t-BOOH, H$_2$O$_2$. Pine pollen, originally extracted with hexane, was reextracted with 70% methanol. The results obtained using the methanol extract, in terms of the antimutagenicity observed in relation to ten kinds of mutagens, showed that it exhibited 17.8, 82.2 and 80.9% inhibitory effects against daunomycin, AFB$_1$, and Trp-P-1, respectively, in Salmonella. typhimurium TA98 and a 72.3% inhibitory effect against AFB$_1$in S. tyPhimurium TA100. In terms of the antimutagenicity exhibited in relation to t-BOOH, a 72.3% inhibitory effect was observed, but no antimutagenicity was observed in relation to the other mutagens and strains. The methanol extract was further fractionated by chloroform, ethyl acetate, n-butanol. In S. typhimurium TA98, the chloroform(150 $\mu\textrm{g}$/plate) fraction showed strong antimutagenic effects of 55.6%, 93.7% and 93.5%, while the ethyl acetate(100 $\mu\textrm{g}$/plate) fraction showed 11.4%, 74.3% and 85.2% in relation to the mutagenicity induced by daunomycin, AFB$_1$and Trp-P-1, respectively. In S. typhimurium TA100, the chloroform and ethyl acetate fractions showed antimutagenic effects of 95.1% and 62.5%, respectively, on the mutagenicity induced by AFB$_1$. In S. typhimurium TA102, the chloroform fraction showed an antimutagenic effect of 93.6% on the mutagenicity induced by t-BOOH.

• Journal of the Korean Society of Food Science and Nutrition
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• v.36 no.2
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• pp.163-173
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• 2007

Lipid peroxidation is one of the main manifestations of oxidative damage and has been found to play an important role in the toxicity and carcinogenesis of many carcinogens. This study was carried out to determine the effects of vitamin C on lipid contents and fatty acid compositions of serum and liver in male rats treated with radiation or aflatoxin $B_1\;(AFB_1)$. Six week-old male Sprague-Dawley rats were randomly divided into 7 groups; control group, radiation exposed group, $AFB_1$ treated group, X-ray and $AFB_1$ co-treated group. Three groups, except control group, were each further divided into vitamin C administered group and not administered groups. For this study, vitamin C was injected with 10 mg/kg of body weight by intraperitoneal injection and 1 hr later, 0.4 mg/kg of $AFB_1$ was injected by the same method. These administrations were repeated every 3 days over a period of 15 days. Only one time, X-ray was irradiated on whole liver with 1,500 cGy. Then vitamin C and AFB1 were administered by the same level and same method described above. On the 16th day of treatments, the animals were sacrificed. From the analysis of the serum lipid patterns, significant decrease (p<0.01) in triglyceride (TG) and total cholesterol levels were observed in X-ray and $AFB_1$ co treated group administered with vitamin C (group 7). In liver lipids, the levels of free cholesterol and total cholesterol were also decreased in X-ray and $AFB_1$ co treated group administered with vitamin C (group 7). The levels of serum free cholesterol and hepatic TG were not significantly different among all groups according to vitamin C administrations. The high density lipoprotein (HDL)-cholesterol level of serum was significantly (p<0.01) increased while the low density lipoprotein (LDL)-cholesterol level was decreased in X-ray and $AFB_1$ co treated group administered with vitamin C (group 7). In the phospholipid fatty-acid compositions of serum and liver tissue, group 3, 5 and 7 showed an increase in polyunsaturated fatty-acid (PUFA) but a decrease in saturated fatty acid (SFA) when compared to the control group. The composition ratio of fatty acid varied according to vitamin C administration. These results suggested that vitamin C has partly suppressive effects on lipid contents and fatty acid composition of serum and liver in rats treated by radiation and $AFB_1$.

• Microbiology and Biotechnology Letters
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• v.24 no.4
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• pp.525-528
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• 1996

To investigate the inhibitory effect of soybean and Korean traditional fermented soybean products on the chemically induced mutagenesis, we extracted soybean, Kanjang, Doenjang, Kochujang, and Chongkukjang with water, methanol and hexane. Inhibitory effect of the extracts was assayed by the SOS chromotest using Escherichia coli PQ37 as a test strain. 4-nitroquinoline-1-oxide(4NQO), N-methyl-N'-nitro-N-nitrosoquanidine(MNNG), and aflatoxin B$_{1}$(AFB$_{1}$) were used as mutagens. Methanol extracts showed relatively higher inhibitory effect than water and hexane extracts. Methanol extracts of soybean, Doenjang, Kochujang, and Chonhkukjang showed inhibitory effect of 68.4, 96.3, 17.5, and 100.9% against MNNG, and 28.6, 109.1, 41.3, and 101.8% against AFB$_{1}$, respectively. Doenjang methanol extract showed inhibitory effect of 51.0, 96.3, and 109.1% against 4NQO, MNNG, and AFB$_{1}$, respectively. Methanol extract of Doenjang showed dose-dependent inhibitory effect against 4NQO, MNNG, and AFB$_{1}$. Inhibitory effect of heat-treated Doenjang and Chongkukjang methanol extracts on the mutagenecity of MNNG and AFB$_{1}$ was remained over 95% of the inhibitory effect of heat-untreated extracts, demonstrating the heat stability of the potent antimutagenic activity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.19 no.2
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• pp.156-162
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• 1990

Antimutagenic effect of doenjag (Korean fermented soy paste) on mutagenesis induced by aflatoxin B1 (AFB1) in Salmonella typhimurium strains TA98 and TA100 was studied. AFB1 revealed maximum mutagenicity at dose level of 1 $\mu$g/plate with metabolic activation system in both strains. Strong antiutagenic activity toward AFB1 was completely inhibited at the level of 50% of the doenjang extract. At the same concentration 64-66% and 39-53% of the AFB1 induced mutageneses were blocked when the methanol extracts of raw and cooked soybeans were added in the system respectively Raw soybeans showed higher ihhibition rate to the mutagenicity than cooked soybeans but the fermented soybeans(doenjang) was the most effective (p<0.05) Other soybean fermented foods such as commercial doenjang natto and miso were also exhibited some antimutagenic activities however the traditional doenjang was the most effective and then commercial doenjang. Natto and miso were less effective.

• Journal of Food Hygiene and Safety
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• v.12 no.4
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• pp.321-327
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• 1997

The antimutagenic effects of juices and methanol extracts from cruciferous vegetables (cabbage, red cabbage, Korean cabbage, kale, cauliflower, broccoli, radish root, leafy radish, rape leaves and shepherd's purse) on the mutagenicity induced by aflatoxin B1(AFB1) and N-methyl-N'-nitrosoguanidine(MNNG) were studied using Salmonella assay system. In the case of juices from the cruciferous vegetables, the juices of cabbage, kale, cauliflower and radish root in the concentrations of 50, 200 and 500 ${mu}ell$/plate considerably decreased the mutagenicity induced by AFB1, and the juices of cabbage and broccoli in the concentrations of 200 and 500${mu}ell$/plate significantly reduced the mutagenicity induced by MNNG. The antimutagenic activities of the juices against AFB1 were stronger than those against MNNG. In the case of methanol extracts from the cruciferous vegetables, the methanol extracts of kale, broccoli and shepherd'purse appeared to inhibit the mutagenicity induced by AFB1 and MNNG in Salmonella typhimurium test strains. The effects of the juices against mutagens quite different from ones of the methanol extracts. The juice of cabbage showed antimutagenicity, but its methanol extract was less effective. However, both juices and methanol extracts from kale and broccoli exhibited strong antimutagenic activities against the mutagens.