Toxicity of menadione in the differentiating human colon carcinoma cell line Caco-2

The human colon adenocarcinoma cell line Caco-2 is susceptible to spontaneo us enterocytic differentiation after reaching confluence and was used on da y 7, 14 and 21 of culture to investigate the toxicity of the quinone menadi one. Menadione was less toxic in day 7 cells compared with the older cell c ultures. Enzymatic activation of menadione and glucose-6-phosphate dehydrog enase activity did not alter during differentiation. Based on these observa tions it was concluded that redoxcycling of menadione occurred at similar l evels throughout differentiation. Further, day 7 cells proved to be more vu lnerable for ATP depletion but had significantly higher levels of intracell ular reduced glutathione than older cells. We conclude that these levels of cellular reduced GSH play a major role in the protection of crypt-like ent erocytic cells. (C) 1999 Elsevier Science Ltd. All rights reserved.