Human variation and risk assessment: microarray and other studies utilizing human hepatocytes and human liver subcellular preparations

J Biochem Mol Toxicol. 2014 Jan;28(1):1-10. doi: 10.1002/jbt.21534. Epub 2013 Nov 22.

Abstract

The new paradigms proposed for human health risk assessment stress the need for the use of human and human-derived cell lines, and this review summarizes the use of primary human hepatocytes and hepatocyte subcellular preparations for the investigation of the metabolism and metabolic interactions of environmental chemicals. This includes interactions based on inhibition, induction, and activation. The role of cytotoxicity is also considered. The use of hepatocytes and hepatocyte preparations provides especially important information for the investigation of human variation and is summarized. This area is, at present, relatively neglected but will in the future be essential for accurate assessment of human health risk. A detailed summary of an initial attempt to utilize microarray technology for the study of genome-wide effects is included.

Keywords: Cytotoxicity; Human Hepatocytes; Human Variation; Microarrays; RNAseq; Toxicant Interactions; Toxicant Metabolism.

Publication types

  • Review

MeSH terms

  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Genetic Variation*
  • Hepatocytes / enzymology
  • Hepatocytes / metabolism*
  • Humans
  • Liver / metabolism*
  • Oligonucleotide Array Sequence Analysis*
  • Risk Assessment*
  • Subcellular Fractions / metabolism*

Substances

  • Enzyme Inhibitors