Bioactivation and toxicity of two anthraquinones in V79 Chinese hamster cells

By Mian, M. - Fratta, D. - Rainaldi, G. - Benetti, D. - Gervasi, P.G.

The role of the flavoprotein NADPH cytochrome P450 reductase, NADH-dehydrogenase and DT-diaphorase in the biotransformation of the anthraquinones rhein and danthron was investigated using purified enzymes, subcellular fractions and cell cultures. The results demonstrated that rhein was more able than danthron to produce O2- by P450 reductase, NADH-dehydrogenase and V79 homogenate and microsomes, and this may explain its higher toxicity to V79 cells. In addition, unlike other quinones, DT-diaphorase appeared not to play a detoxication role in rhein and danthron biotransformation. On the contrary, by inhibiting DT-diaphorase with dicoumarol, the rhein- and danthron-derived cytotoxicity in V79 cells was reduced. This finding suggests that, for these quinones, other coumarol-sensitive biotransformation routes are operative in V79 cells.