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

Abstract

PTU and its analogues effectively suppress melanogenesis by inhibiting tyrosinase activity as Cu-chelators (3, 16); they also inhibit acetylcholine esterase activity (12), alter dynein ATPase activity as an SH-reagent (4) and induce pulmonary oedema (29). In addition to these different biological activities, Eguchi and his colleagues found that PTU effectively accelerates the transdifferentiation of retinal PECs from chick embryos (7,8,9,19). It is still not clear, however, what activity of this substance is basically responsible for the enhancement of transdifferentiation in PECs in vitro. In the process of analyzing the mechanism of the transdifferentiation of PECs in vitro, we discovered an as yet unreported PTU activity : 0.5 mM PTU stimulated the uptake of exogenous Cu by PECs and enhanced the cytotoxic effect of Cu about 40-fold.The study reported here was made to characterize this new activity of PTU and its analogues as a means to determining the mechanisms of PTU effects on the various biological phenomena cited above and to investigating the toxic effect of Cu on cells.

Characterization of and Mechanism for Copper-Induced Thioureation of Serum Albumin

“…However, high levels of Tus are intrinsically toxic physiologically − . It is noteworthy that the combination of copper with Tus (e.g., phenylthiourea, ANTU, and pyrrolidine dithiocarbamate) was much more toxic than copper or Tus alone for cultured cells , . The treatment of these cells with copper-binding protein such as albumin would decrease the cytotoxic effect .…”