Phenylthiourea enhances Cu cytotoxicity in cell cultures: Its mode of action.

Abstract

PTU [phenylthiourea] enhanced the cytotoxic effects of CuCl2 on chick embryonic PEC [pigmented epithelial cells] cultured in vitro. Most PEC maintained in medium containing 0.5 mM PTU were lysed within 4 h by the addition of 0.1 mM CuCl2, which killed no PEC in the absence of PTU. The effect of PTU was not specific to PEC. All cell lines tested (human oral carcinoma KB cell, mouse neuroblastoma N-18 cell, mouse N-115 cell and mouse melanoma B-16 cell) reacted against exogenous Cu in the presence of PTU as did the PEC. Analogs of PTU had effects on PEC similar to those on PTU in the presence of Cu ion, ANTU [.alpha.-naphthylthiourea] had a greater effect than PTU. MTU [N-methylthiourea] and TU [thiourea] had less effect than PTU. PTU did not affect the cytolysis induced by the addition of the divalent cations Mn, Co and Zn. About 6-fold the 64Cu-uptake by PEC was scored in the presence of PTU. The relation between this cytotoxic-enhancing effect and other biological activities of PTU were discussed.