Cytotoxicity of alkyl-lysophospholipid derivatives and low-alkyl-cleavage enzyme activities in rat brain tumor cells.
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| Abstract |
Alkyl-lysophospholipids (ALP) and related derivatives inhibited the in vitro incorporation of [3H]thymidine into seven different permanent cell lines derived from rat brain tumors. The cytostatic effect of ALP was dependent on dosage and incubation time. Naturally occurring 2-lysophosphatidylcholine did not exhibit cytostatic effects; under these conditions, the incorporation rates of [3H]thymidine were generally more than 100% of the controls. The trypan blue dye exclusion test, which was used to assess severe cell damage, correlated with the extent that [3H]thymidine incorporation was inhibited by ALP. Preincubation of ALP (rac-1-octadecyl-lyso-glycero-3-phosphocholine) for more than 8 min with a tetrahydropteridine-dependent O-alkyl cleavage enzyme preparation from rat liver microsomes destroyed almost all of the cytotoxic properties of ALP when tested at a concentration that previously inhibited tumor growth by more than 50%. [3H]Thymidine incorporation rates were greater than 100% for astrocytoma cells incubated with ALP after exposure to the alkyl cleavage enzyme. Comparison of the microsomal activities of the tetrahydropteridine-dependent alkyl-cleavage enzyme present in astrocytoma 78-FR-G-299 cells and the pleomorphic glioma 78-FR-G-219/S4 cells to that found in normal skin fibroblasts and rat livers revealed a markedly reduced activity in the neoplastic cell lines. Moreover, those tumor cells that were more resistant to ALP cytotoxicity (pleomorphic glioma, 78-FR-G-219/S4) had a 3-fold higher tetrahydropteridine-dependent cleavage activity than a more cytotoxic sensitive line (astrocytoma cells, 78-FR-G-299). Our results indicate that the low-alkyl-cleavage enzyme activities in these neoplastic cells in comparison to normal cells might be a factor in explaining the relatively high cytotoxicity of ALP in tumor cells.
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| Authors | W E Berdel, E Greiner, U Fink, D Stavrou, A Reichert, J Rastetter, D R Hoffman, F Snyder |
| Journal | Cancer research (Cancer Res) Vol. 43 Issue 2 Pg. 541-5 (Feb 1983) ISSN: 0008-5472 [Print] United States |
| PMID | 6848177 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.) |
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