Effect of a Dithiol on Survival Time after Irradiation

Abstract

CONTRARY to previous reports¹, Doherty et al. ² obtained partial protection of X-irradiated mice with 2,3-dimercaptopropanol. If a foreign dithiol compound is effective perhaps the dithiol form of an essential metabolite might also prove beneficial in radiation injury. Mice were exposed to 550 r. acute whole body X-irradiation under our usual conditions³. The animals received 50 mgm./kgm. of DL-6,8-dithioloctanoic acid, the reduced form of thioctic acid, according to the schedule in Table 1. It is evident that the compound significantly increased the ST50 day, particularly if administered prior to irradiation. However, it has no real effect in reducing total mortality. The mechanisms involved in such partial protection are obscure, but dithiols are known to form resonance-stabilized radicals which could interact with the various oxidizing radicals produced by ionizing radiation. Such reactions could be continuous until the dithiol was completely destroyed. If the proportion of dithiol to oxidizeis was in favour of the latter, this could explain the increased ST50 day and the unaffected total mortality observed in the group receiving the dithiol immediately prior to irradiation. Pre-irradiation medication could also result in protection of radiosensitive groups in the tissues by direct combination, but it might be difficult to obtain complete coverage. Post-irradiation medication could assist in breaking the chain reaction involving organic peroxides⁵ but still not prevent the early damage which would tend to decrease total survival. Thus it would appear that a dithiol can increase survival time, possibly by the above mechanisms, yet give no permanent protection against the lethal effects of ionizing radiation.