Non-linear relationships between aflatoxin B1 levels and the biological response of monkey kidney vero cells

Authors: Rasooly, Reuven; Hernlem, Bradley - Brad; He, Xiaohua

Submitted to: Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/2/2013
Publication Date: 8/14/2013
Publication URL: http://handle.nal.usda.gov/10113/58733
Citation: Rasooly, R., Hernlem, B.J., He, X. 2013. Non-linear relationships between aflatoxin B1 levels and the biological response of monkey kidney vero cells. Toxins. 5:1447-1461. doi:10.3390/toxins5081447.

Interpretive Summary: The aflatoxins (AF) are a group of toxic chemicals produced by fungi that frequently contaminate food and feed. These toxins cause animal and human illnesses, reduce growth rate and feed conversion in livestock and decrease milk production. Most human exposure to AF occurs by eating contaminated animal products such as meat, eggs, and dairy. AF accumulates in the liver and can cause liver cancer, cirrhosis, or direct liver damage. Even though many countries seek to limit exposure to AF, and there are no clear safe feeding levels, recently the FDA has allowed the blending and dilution of AF contaminated grain with uncontaminated grain for use as animal feed. This policy assumes that low levels of AF in feed which are not toxic to the animal are of no further concern. In the present study we developed methods to measure active AFB1, a type of the most potently genotoxic and carcinogenic AF. In contrast to high levels of AFB1, which decrease cellular activity, we show here that low levels of AFB1 have an opposite, stimulatory effect on animal cells. This suggests that the effects of low levels of AF are complex and may have unknown biological effects. This research has implications to livestock and food safety, as well as to understanding the effects of AF exposure.

Technical Abstract: Aflatoxin (AF)-producing fungi contaminate food and feed during preharvest, storage and processing periods. Once consumed, AF accumulates in tissues, causing illnesses in animals and humans. At least 20 different types of AFs have been identified, and of these, aflatoxin B1 (AFB1) is the most ubiquitous and the most potently genotoxic and carcinogenic. It has been postulated that most human exposure to AFs is as a result of consumption of contaminated animal products. Even though there are no clear safe feeding levels of AFs, attempts have been made to limit exposure to AFs. Recently the FDA has allowed the blending and dilution of grain containing higher levels of AFs with uncontaminated grain for use as animal feed. This policy implicitly assumes that the deleterious effects of AFs are linearly correlated to concentration, and the assumption involves extrapolation of these levels of AFs in feed, which are not toxic to the animal and are of no further concern. In the present study we developed quantitative methods for the detection of biologically active AFB1, which demonstrate that there is a nonlinear dose response relationship at the cellular level. AFB1 at low concentrations has an opposite effect from higher doses that inhibit protein synthesis. Therefore, we cannot use the effects at higher concentrations to predict the effects of low levels of AF.