DETOXIFIED VENOM FROM CROTALUS-DURISSUS-TERRIFICUS IS DEVOID OF CYTOTOXIC ACTIVITY AND INDUCES MITOGENESIS

The venom from the snake Crotalus durrissus terrificus was detoxified by stepwise incorporation of stable cationic iodine. The venoid, in a dosage equivalent to 100 LD(50) of the letal venom, was injected in mi ce without lethal exits. The native venom (NAT), or its toxoided (TXD) derivative were incubated in presence or absence of mitogens, with hu man mononuclear (MN), B and T cells, with a pulse of [H-3]Thymidine. N o synergistic or antagonistic effects were observed in the combined ac tivity of the mitogens and NAT or TXD. In the direct action of NAT the incorporation of radioactivity into MN and T cells diminished with ve nom increase in concentration indicating that the cytotoxicity of the native venom was correlated with the amount added. With B cells, the n ative venom exercised an initial mitogenic activity, declining in the higher concentration. On the other hand, the TXD showed a consistent e ffect, increasing the thymidine uptake in a manner related to concentr ation. This stimulation by TXD was observed with all groups of cells. The results indicate that, by abolishing direct cytotoxic activity wit h toxoiding of this venom, a derivative that enhances mitogenesis in t hese white cells can be obtained.