Experiments in mice showed that intraperitoneal (i.p.) injection of unithiol (sodium salt of 2,3- dimercapto-l-propanesulfonic acid) diminished toxicity of several aminothiol radioprotectors, increasing the LD50 of cystamine by 40% and aminoethanisothiuronium bromide hydrobromide (AET) by 64%. The optimum ratio for the doses is 0.5 molar equivalent of unithiol per radioprotective thiol. A new radioprotector (mixed disulfide of cysteamine and unithiol--MDCU) has a weak toxicity: the LD50 is 750 mg/kg i.p. The use of unithiol makes it possible to increase the dose of the SH-radioprotectors, enhancing the dose reduction factor (DRF) of cystamine and AET by 30% for x-ray irradiation. A somewhat lesser effect is observed with fission neutron irradiation. The DRF of MDCU is equal to 1.6 for x-ray irradiation and is 1.1 for neutron irradiation. The mechanism of antitoxic action of unithiol could not be detected in Chinese hamster fibroblasts. It may be caused by the competition of unithiol and the SH-radioprotectors for certain, as yet undetermined, biochemical structures in brain neurons. It is also possible that unithiol may decrease penetration of SH-radioprotectors into the brain.
AFRRI Contract Report 97-1; DNA001-93-C-0155