The cytotoxicity of methylmercuric hydroxide and colchicine in cultured mouse neuroblastoma cells

After a 24-hr growth period in unsealed flasks, uncloned C1300 mouse neuroblastoma cells were exposed to either methylmercuric hydroxide (CH₃HgOH) (3 × 10^?9 –3 × 10^?6m) or colchicine (3 × 10^?10–1 × 10^?7m) in nutrient mixture F-12 (Ham) for 24–72 hr in sealed flasks. After 48 hr, CH₃HgOH (1 × 10^?6m) produced a 50% decrease in the number of morphologically differentiated cells and a significant increase in cell sloughing without inhibiting cell division or decreasing cell viability. However, after 48 hr, colchicine inhibited cell division and morphological differentiation at concentrations lower than those that caused increased cell sloughing or decreased cell viability. When CH₃HgOH (1 × 10^?6m) was replaced with control medium after 24 hr, most cytotoxic effects were reversed. The toxic effects were not as readily reversed after exposure to CH₃HgOH for 48 hr. Sloughed cells did not survive 48 hr exposure to CH₃HgOH when replaced in the control medium although they did survive after a 24-hr exposure. Recovery from the cytotoxic effects of CH₃HgOH was reduced in the presence of 3 × 10^?6m cycloheximide. It is concluded that CH₃HgOH exerts its toxicity at several sites within the neuroblastoma cell. Although the organomercurials have been shown to bind to neurotubles, the cytotoxicity of CH₃HgOH in neuroblastoma cells can not be ascribed solely to this mechanism. Recovery from the effects of short-term exposure may involve the synthesis of new protein.