Radiation protection by alpha-methyl-homocysteine thiolactone in vitro.
The radiation protective effect of thiol compounds is unequivocal and their use is only limited by their toxic effects. We used the principle of alpha alkylation, which renders amino acids unmetabolizable, to reduce the toxicity of homocysteine. This product, alpha-methyl-homocysteine thio-lactone, was tested for toxicity and radiation protective effect along with known protectors L-cysteine, cysteamine and WR 1065 in cell culture using V79-4 Chinese hamster lung cells. The three-day growth 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 reproductive integrity, were carried out and revealed that GL-2 had no adverse effects in this test system. Radiation protection tests showed that GL-2 exhibited protective activity against radiation induced lethality above that seen with cysteine and cysteamine, but below WR 1065. However, GL-2 showed little or no negative effects toward the cell itself, in direct contrast to WR 1065. Our findings show a potentially important tool and principle to reduce toxicity of radiation protectors with analogous structures.
Koch
K E
KE
University of Utah, Dpt Medicinal Chemistry, Salt Lake City, UT, USA.
Roberts
J C
JC
Lubec
G
G
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002588:Cesium Radioisotopes; D006224:Cricetinae; D003412:Cricetulus; D003543:Cysteamine / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D008624:Mercaptoethylamines / Q000494:pharmacology; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D011837:Radiation-Protective Agents / Q000494:pharmacology* / Q000633:toxicity
D002588:Cesium Radioisotopes; D008624:Mercaptoethylamines; D011837:Radiation-Protective Agents; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D006710:Homocysteine; C104256:alpha-methylhomocysteine thiolactone; D003543:Cysteamine; D003545:Cysteine