scholarly journals Prenatal exposure of mice to the human liver carcinogen aflatoxin B1reveals a critical window of susceptibility to genetic change

2014 ◽  
Vol 136 (6) ◽  
pp. 1254-1262 ◽  
Author(s):  
Supawadee Chawanthayatham ◽  
Apinya Thiantanawat ◽  
Patricia A. Egner ◽  
John D. Groopman ◽  
Gerald N. Wogan ◽  
...  
Toxins ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 625 ◽  
Author(s):  
Thilona Arumugam ◽  
Terisha Ghazi ◽  
Anil Chuturgoon

Fumonisin B1 (FB1), a Fusarium-produced mycotoxin, is found in various foods and feeds. It is a well-known liver carcinogen in experimental animals; however, its role in genotoxicity is controversial. The current study investigated FB1-triggered changes in the epigenetic regulation of PTEN and determined its effect on DNA damage checkpoint regulation in human liver hepatoma G2 (HepG2) cells. Following treatment with FB1 (IC50: 200 µM; 24 h), the expression of miR-30c, KDM5B, PTEN, H3K4me3, PI3K, AKT, p-ser473-AKT, CHK1, and p-ser280-CHK1 was measured using qPCR and/or Western blot. H3K4me3 enrichment at the PTEN promoter region was assayed via a ChIP assay and DNA damage was determined using an ELISA. FB1 induced oxidative DNA damage. Total KDM5B expression was reduced, which subsequently increased the total H3K4me3 and the enrichment of H3K4me3 at PTEN promoters. Increased H3K4me3 induced an increase in PTEN transcript levels. However, miR-30c inhibited PTEN translation. Thus, PI3K/AKT signaling was activated, inhibiting CHK1 activity via phosphorylation of its serine 280 residue preventing the repair of damaged DNA. In conclusion, FB1 epigenetically modulates the PTEN/PI3K/AKT signaling cascade, preventing DNA damage checkpoint regulation, and induces significant DNA damage.


2016 ◽  
Vol 80 (1) ◽  
pp. 44-49 ◽  
Author(s):  
YA XU ◽  
ANDREW DOEL ◽  
SINEAD WATSON ◽  
MICHAEL N. ROUTLEDGE ◽  
CHRISTOPHER T. ELLIOTT ◽  
...  

ABSTRACTAflatoxin, a human liver carcinogen, frequently contaminates groundnuts, maize, rice, and other grains, especially in Africa. The aim of this study was to evaluate the effectiveness of an educational intervention that involved training rural Gambian women on how to identify and remove moldy groundnuts to reduce aflatoxin B1 (AFB1) contamination. In total, 25 women, recruited from the West Kiang region of The Gambia, were trained on how to recognize and remove moldy groundnuts. Market-purchased groundnuts were hand sorted by the women. Groundnuts were sampled at baseline (n =5), after hand sorting (“clean,” n =25 and “moldy,” n =25), and after roasting (n =5). All samples were analyzed for AFB1 by enzyme-linked immunosorbent assay. A reduction of 42.9% was achieved based on the median AFB1 levels at baseline and after hand sorting (clean groundnuts), whereas an alternative estimate, based on the total AFB1 in moldy and clean groundnuts, indicated a reduction of 96.7%, with a loss of only 2% of the groundnuts. By roasting the already clean sorted groundnuts, the AFB1 reduction achieved (based on median levels) was 39.3%. This educational intervention on how to identify and remove moldy groundnuts was simple and effective in reducing AFB1 contamination.


Nutrients ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1532 ◽  
Author(s):  
Grace Odongo ◽  
Nina Schlotz ◽  
Susanne Baldermann ◽  
Susanne Neugart ◽  
Susanne Huyskens-Keil ◽  
...  

Plant cultivation and processing may impact nutrient and phytochemical content of vegetables. The present study aimed at determining the influence of cultivation and processing on the health promoting capacity of African nightshade (Solanum scabrum Mill.) leaves, an indigenous vegetable, rich in nutrients and phytochemicals. Anti-genotoxicity against the human liver carcinogen aflatoxin B1 (AFB1) as determined by the comet assay and radical oxygen species (ROS) scavenging capacity of ethanolic and aqueous extracts were investigated in human derived liver (HepG2) cells. ROS scavenging activity was assessed using electron paramagnetic spin resonance and quantification of ARE/Nrf2 mediated gene expression. The cultivation was done under different environmental conditions. The processing included fermentation and cooking; postharvest ultraviolet irradiation (UV-C) treatment was also investigated. Overall, S. scabrum extracts showed strong health promoting potential, the highest potential was observed with the fermented extract, which showed a 60% reduction of AFB1 induced DNA damage and a 38% reduction in FeSO4 induced oxidative stress. The content of total polyphenols, carotenoids and chlorophylls was indeed affected by cultivation and processing. Based on the present in vitro findings consumption of S. scabrum leaves could be further encouraged, preferentially after cooking or fermentation of the plant.


Author(s):  
C. Uphoff ◽  
C. Nyquist-Battie

Fetal Alcohol Syndrone (FAS) is a syndrome with characteristic abnormalities resulting from prenatal exposure to ethanol. In many children with FAS syndrome gross pathological changes in the heart are seen with septal defects the most prevalent abnormality recorded. Few studies in animal models have been performed on the effects of ethanol on heart development. In our laboratory, it has been observed that prenatal ethanol exposure of Swiss albino mice results in abnormal cardiac muscle ultrastructure when mice were examined at birth and compared to pairfed and normal controls. Fig. 1 is an example of the changes that are seen in the ethanol-exposed animals. These changes include enlarged mitochondria with loss of inner mitochondrial membrane integrity and loss of myofibrils. Morphometric analysis substantiated the presence of these alterations from normal cardiac ultrastructure. The present work was undertaken to determine if the pathological changes seen in the newborn mice prenatally exposed to ethanol could be reversed with age and abstinence.


Xenobiotica ◽  
2009 ◽  
Vol 00 (00) ◽  
pp. 090901052053001-8
Author(s):  
K. Murai ◽  
H. Yamazaki ◽  
K. Nakagawa ◽  
R. Kawai ◽  
T. Kamataki

Author(s):  
Rajesh Lamichhane ◽  
Fran Munro ◽  
Thomas W. R. Harrop ◽  
Sara M. Harpe ◽  
Peter K. Dearden ◽  
...  

2000 ◽  
Vol 86 (5) ◽  
pp. 215-221 ◽  
Author(s):  
Paivi Taavitsainen ◽  
Markku Anttila ◽  
Leena Nyman ◽  
Hari Karnani ◽  
Jarmo S. Salonen ◽  
...  

1997 ◽  
Author(s):  
William F. Bosron ◽  
Robert A. Dean ◽  
Monica R. Brzezinski ◽  
Evgenia V. Pindel
Keyword(s):  

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