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

J Immunotoxicol. Apr-Jun 2015;12(2):194-8. doi: 10.3109/1547691X.2014.925994. Epub 2014 Jul 16.

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.

Keywords: AFB1; AKR-7A2; GST-M1; lymphocytes; monocytes.

MeSH terms

  • Aflatoxin B1 / pharmacology*
  • Aldehyde Reductase / genetics
  • Aldehyde Reductase / metabolism*
  • Cell Cycle / drug effects
  • Gene Expression Regulation
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism*
  • Hep G2 Cells
  • Humans
  • Lymphocytes / drug effects*
  • Lymphocytes / immunology
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Transcription, Genetic / immunology

Substances

  • Aflatoxin B1
  • aflatoxin B1 aldehyde reductase
  • AKR7A3 protein, human
  • Aldehyde Reductase
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1