MODULATION OF RADIATION-INDUCED APOPTOSIS BY THIOLAMINES

Exposure to the thiolamine radioprotector N-(2-mercaptoethyl)-1,3-prop anediamine (WR-1065) induced apoptosis in the mouse TB8.3 hybridoma af ter a 60-min (LD50 = 4.5 mM) or during a 20-h (LD50 = 0.15 mM) exposur e. In contrast, a 20-h exposure to 17 mM L-cysteine or 10 mM cysteamin e was required to induce 50% apoptosis within 20 h. Apoptosis was nor induced by either a 60-min or 20-h exposure to 10 mM of the thiazolidi ne prodrugs ribose-cysteine (RibCys) or ribose-cysteamine (RibCyst). T hiolamine-induced apoptosis appeared to be a p53-independent process s ince it was induced by WR-1065 exposure in human HL60 cells. Exposure to WR-1065 (4 mM for 15 min) or cysteine (10 mM for 60 min) before and during irradiation protected cells against the induction of both DNA double-strand breaks and apoptosis, while exposure to RibCys (10 mM fo r 3 h) did not. Treatment with either WR-1065, cysteine, RibCys or Rib Cyst for 60 min beginning 60 min after irradiation did not affect the level of radiation-induced apoptosis. In contrast, treatment with eith er cysteine, cysteamine or RibCys for 20 h beginning 60 min after irra diation enhanced radiation-induced apoptosis. Similar experiments coul d not be conducted with WR-1065 because of its extreme toxicity. Our r esults indicate that thiolamine enhancement of radiation-induced apopt osis is not involved in their previously reported capacity to reduce r adiation-induced mutations.