Effects of arsenic trioxide on blastogenesis in mice lymphocytes

with special reference to synthesis of DNA, RNA or protein

Abstract

This study attempts to clarify the toxicity of As₂O₃ at the cellular level. Phytohemaggulutinin (PHA) and concanavalin A (Con A), both of which are mitogenic activators, stimulate blastogenesis in lymphocytes taken from the spleens of mice. Measuring the uptake of ³H-thymidine (³H-T), ³H-uridine (³H-U) or ³H -Leucine (³H-L), stimulated by PHA or Con A, has been used as a method of observing DNA, RNA or protein synthesis of lymphocytes and the influences of As₂O₃ on this synthesis was investigated by administration of various amounts of As₂O₃ in vitro (addition of 1 -100μg/ml) and in vivo (oral administration of 0.1-10 mg/kg).
As a result, the addition of more than 3μg/ml of As₂O₃ in vitro remarkably inhibited the uptake of ³H-T, ³H-U or ³H-L. Increasing doses of As₂O₃ in vivo inhibited the uptake of ³H -T with a dose response, especially strongly in adminitration of more than 5 mg/kg of As₂O₃. However, administrationof each dose of As₂O₃ in vivo produced little or no inhibitory effect on the uptake of ³H -U and ³H-L.
This study suggests that As₂O₃ may interfere with the blastogenesis of lymphocytes derived from mice spleen and it has especially a strong inhibitory action on the DNA synthesis system.