2-[(Aminopropyl)amino]ethanethiol (WR1065) is anti-neoplastic and anti-mutagenic when given during 60Co gamma-ray irradiation.
We have studied the effect of 2-[(aminopropyl)amino]ethanethiol (WR1065) on the induction of neoplastic transformation using 10T1/2 cells and on mutation at the hypoxanthine guanine phosphoribosyl transferase (HGPRT) locus using Chinese hamster V79 cells. Here we report the first observations that treatment of 10T1/2 cells with 1 mM WR1065 for a total of 35 min during irradiation with 60Co gamma-rays significantly reduces the incidence of neoplastic transformation while having no effect on cell viability. In a similar experiment with V79 cells in which 4 mM WR1065 was used, we found a significant reduction in mutation frequency at the HGPRT locus and significant protection against cell killing. These results suggest that WR1065 acts to modulate both acute damage and sub-lethal processes that lead to mutation and neoplastic transformation. Beyond the purely mechanistic approach of these studies, the potential application of these agents to minimizing the long-term neoplastic effects of radiation or chemotherapeutic agents currently in use for treating potentially curable cancer patients should be further investigated.
Hill
C K
CK
Nagy
B
B
Peraino
C
C
Grdina
D J
DJ
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects; D003037:Cobalt Radioisotopes; D006224:Cricetinae; D003412:Cricetulus; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008624:Mercaptoethylamines / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D009154:Mutation
D003037:Cobalt Radioisotopes; D008624:Mercaptoethylamines; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D007041:Hypoxanthine Phosphoribosyltransferase