The radiation protective effect of thiol compounds is unequivocal and
their use is only limited by their toxic effects. We used the principl
e of alpha alkylation, which renders amino acids unmetabolizable, to r
educe the toxicity of homocysteine. This product, alpha-methyl-homocys
teine thio-lactone, was tested for toxicity and radiation protective e
ffect along with known protectors L-cysteine, cysteamine and WR 1065 i
n cell culture using V79-4 Chinese hamster lung cells. The three-day g
rowth curve assays, useful to measure overall effects on cell growth,
revealed lowest toxicity for alpha-methyl-homocysteine thiolactone (GL
-2). Clonogenic survival tests, used to evaluate the retention of repr
oductive integrity, were carried out and revealed that GL-2 had no adv
erse effects in this test system. Radiation protection tests showed th
at GL-2 exhibited protective activity against radiation induced lethal
ity above that seen with cysteine and cysteamine, but below WR 1065. H
owever, GL-2 showed little or no negative effects toward the cell itse
lf, in direct contrast to WR 1065. Our findings show a potentially imp
ortant tool and principle to reduce toxicity of radiation protectors w
ith analogous structures.