Human Variation and Risk Assessment: Microarray and Other Studies Utilizing Human Hepatocytes and Human Liver Subcellular Preparations

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.

Determination of Metabolic Stability Using Cryopreserved Hepatocytes from Rainbow Trout (Oncorhynchus mykiss)

“…Isolated hepatocytes obtained from mammals have long been used in drug discovery and chemical hazard assessment (Houston, 1994;Obach, 1999;Hengstler et al, 2000;Gomez-Lechon et al, 2003;Hewitt et al, 2007;Hodgson et al, 2014). Although their preparation can be more cumbersome, hepatocytes offer several advantages over other in vitro systems derived from liver tissue, such as S9 fractions and microsomes.…”