GST-M1 is transcribed moreso than AKR7A2 in AFB₁-exposed human monocytes and lymphocytes

Abstract

Glutathione-S-transferases (GST) and aldo-keto reductases (AKR) are key aflatoxin (AF)-detoxifying enzymes. In this study, the expression of GST-M1, GST-T1, AKR-7A2, and AKR-7A3 genes in human monocytes and lymphocytes was analyzed after in vitro exposure to 10 or 100 ng AFB₁/ml for 2 h. Unlike in pilot studies that showed that all four examined genes were present in HepG2 cells, in lymphocytes and monocytes, only GST-M1 and AKR-7A2 were detected. In fact, the induced expression of both GST-M1 and AKR-7A2 genes in human monocytes was moreso than that seen in AFB₁-exposed lymphocytes. In addition, analyses of the effects of the exposures on cell cycle status were performed as, in cells lacking adequate detoxification capacities, it would be expected the cells would arrest at checkpoints in the cell cycle or progress to apoptotic/necrotic states. The results here indicated that only the high dose of AFB₁ led to a change in cell cycle profiles and only in the monocytes (i.e. cells in S phase were significantly reduced). In general, the results here strongly suggest that human immune cell lineages appear to be able to increase their expression of AFB₁-detoxifying enzymes (albeit to differing degrees) and, as a result, are able to counter potential toxicities from AFB₁ and (likely) its metabolites.

• AFB₁
• AKR-7A2
• GST-M1
• lymphocytes
• monocytes

Acknowledgements

The authors wish to acknowledge the Ferdowsi University of Mashhad bureau (area) for research and technology. We also thank N. Tabasi, N. Ghasemi, and S. Zamani Taghizadeh Rabe for their technical assistance.