Phenylthiourea enhances Cu cytotoxicity in cell cultures: its mode of action

PTU markedly enhanced the cytotoxic effects of CuCl2 on chick embryonic PECs cultured in vitro. We investigated this newly discovered effect of PTU and its analogues in relation to the toxic effects of Cu ion. Most PECs maintained in medium containing 0.5 mM PTU were lysed within 4 h by the addition of 0.1 mM CuCl2, which addition killed no PECs in the absence of PTU. The effect of PTU was not specific to PECs. All the cell lines tested, KB, N-18, N-115 and B-16, reacted against exogenous Cu in the presence of PTU as did the PECs. Analogues of PTU had effects on PECs similar to those on PTU in the presence of Cu ion. ANTU had a greater effect than PTU. MTU and TU 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 PECs was scored in the presence of PTU. The relation between this cytotoxic-enhancing effect and other biological activities of PTU are discussed.