Use of Cultured Hepatoma Cell Lines in the Assessment of Aldehyde Metabolism

Abstract

Aldehyde dehydrogenases (ALDH) represent a major pathway for the enzymatic removal of many potentially toxic aldehydes. The purpose of this study was to examine the basal levels of ALDH in five hepatoma cell lines chosen as representatives of three different species (man, rat, mouse) and their inducibility by some xenobiotics. Human HepG2, rat MH1C1, HTC, H4IIEC3 and mouse Hepa 1c1c7 cell lines were grown as monolayers. The ALDH activities were determined in cell homogenates from both unexposed control cultures and cells exposed to phenobarbital (PB), 3-methylcholanthrene (MC) and β-naphthoflavone (BNF). The ALDH activity was detected using benzaldehyde (BA) and propionaldehyde (PA) as substrates and both NAD and NADP as co-enzymes.Great variability in basal ALDH levels was found in the five cell lines: BA/NAD and BA/NADP enzyme activities were very high in the HTC cell line, intermediate in MH1C1 cells (near to normal rat hepatocytes) and very low in the remaining three cell lines. In HTC cells only, the PA/NAD activity was slightly induced by PB, but it remained unchanged under all the other experimental conditions. MH1C1 cells showed highly significant increases of all the activities with MC and BNF (up to 10-fold). The low basal activity of the H4IIEC3 cell line was significantly increased by MC and BNF, but only with BA/NADP. The Hepa 1c1c7 cell line responded only to BNF, as inducing compound, whereas the low basal enzyme levels of the human-derived HepG2 cell line were not significantly increased.These results suggest various applications of hepatoma cell cultures in in vitro toxicology.