Assessing indirect agent-induced gene toxicity

Notably, uncovering of genotoxicity is not always straightforward, but requires specific solutions. Some agents develop their toxic effects only when metabolized in particular organs; this is especially common in liver cells. These ingredients, initially considered harmless to the DNA turn out to be dangerous genotoxic substances. Not only drugs, but also food contaminants often develop toxicity by metabolic activation in the liver. In the case of aflatoxin B1, a toxin from widespread Aspergillus fungi, the detoxification mechanisms of the human liver work as an agitator: the aflatoxin B1 oxidation yields an extremely DNA reactive compound, which results in gene mutation. Aflatoxin metabolites are largely responsible for the rise of liver cancer worldwide.

For the in vitro genotoxicity risk assessment, the human-derived liver cell line, HepaRG^TM is an excellent model for mapping the metabolic response of human hepatocytes (1, 2). HepaRG™ cells naturally lend themselves to OECD validated in vitro genotoxicity testing. In a recent study, 3T has shown that AUREA gTOXXs reliably detects DNA strand breaks in HepaRG^TM cells that have been exposed to aflatoxin B1 (3). With the combination of the HepaRG^TM cell line and the AUREA gTOXXs solution, 3T GmbH & Co.KG is breaking new ground in in vitro ‚Genotox‘ risk assessment. Importantly, the risk assessment of DNA strand break over time by gTOXXs testing reports not only on the DNA damage, but also the repair capacity. This unique feature provides valuable insights into the physiological state of the HepaRG^TM cells.

The rapid risk assessment of the genotoxic potency of pro-toxicants at an early stage of your product development by AUREA gTOXXs with HepaRG^TM yields several valuable advantages:

• Fast and standardized procedures of risk assessment using the human hepatocyte cell line HepaRG^TM
• High kinetic resolution of DNA damage and repair activity
• Costs and time savings in the early stages of product development and scientific research

Conclusion: The automated gTOXXs solution differentiates the risk potential of liver metabolites in HepaRG^TM with high degree of scalability and certainty with fast, reliable and robust results.

Safe and increasingly animal-free products can be developed thanks to risk assessment by AUREA gTOXXs!  

1. Wang S, Wang M et al. 2018. Toxins (Basel) 10 pii E154.
2. Murayama N, Yamazaki H. 2018. J Toxicol Sci, 43:241-245
3. Dressler D, Pfitzner I et al. 2018. SOT 57^th Meet ToXExpo, San Antonio, March 11^th -15^th