Cytoprotection by somatostatin of normal and malignant clonogenic cells against the in vitro cytotoxicity of bischloroethylnitrosourea (BCNU).
The various pharmacological effects of somatostatin may be explained by the hypothesis that the paracrine peptide, by "stabilizing" cell membranes, inhibits the secretion of hormones as well as protects other cells (vascular endothelium, parenchyma) from different lesions (vasculo-, organo-, cytoprotection). This hypothesis was tested in vitro, using bischloroethyl-nitrosourea (BCNU)-intoxicated stem cells of normal mouse granulopoiesis and of the L 1210 leukemia. Clonogenic mouse bone marrow and L 1210 cells were grown in agar-containing glass capillaries. Using these colony assays and a ID90 of BCNU, cyclic somatostatin influenced the BCNU-cytotoxicity neither at simultaneous nor at subsequent application. However, when given 2 h prior to BCNU, the inhibition of colony growth was almost totally abolished. This cytoprotective effect was seen with normal granulopoietic as well as with leukemic cells. The effect did not show up, if the inactive linear somatostatin was used. N-acetyl-cysteine, a SH-compound applied as a chemoprotective adjunct, did not reveal a cytoprotective effect under identical experimental conditions, either. The results were discussed in view of common efforts to reduce the toxicity of cancer chemotherapy.
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002330:Carmustine / Q000627:therapeutic use / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002999:Clone Cells; D006098:Granulocytes / Q000187:drug effects; D007939:Leukemia L1210 / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D013004:Somatostatin / Q000494:pharmacology*
D013004:Somatostatin; D002330:Carmustine; D000111:Acetylcysteine