ABSTRACT

To date the most available source of proliferating cells are those cell-lines initially derived from well-differentiated hepatocellular tumours, such as HepG2 cells. They are readily available and proliferate well in culture, theoretically therefore being available in unlimited quantities. However, as with all tumour-derived cells, proliferation is associated with a relative loss of some differentiated function. In general-and particularly if the culture conditions are optimized as we describe below-synthesis of many proteins can be achieved at in vivo equivalent levels, but there are important relative defi cits particularly in detoxifi catory functions. Transcripts of CYP3A4 are present in HepG2 cells although mRNA levels are far lower (100-1000 fold) than in adult primary human hepatocytes (Kenny et al. 2008) although there is a large inter-individual variability between cells from livers from different individuals (Wilkening et al. 2003, Donato et al. 2007). Interestingly our data demonstrated that microsomes extracted from Hep G2 cells, and also that HepG2 cells cultured in optimal matrix confi gurations, could show CYP 450 activity within the lower tertile of that of a panel of human primary human hepatocytes.