This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Aida, T. Articles by Bodell, W. J. Search for Related Content PubMed PubMed Citation Articles by Aida, T. Articles by Bodell, W. J.

Effect of Caffeine on Cytotoxicity and Sister Chromatid Exchange Induction in Sensitive and Resistant Rat Brain Tumor Cells Treated with 1,3-Bis(2-chloroethyl)-1-nitrosourea¹

Brain Tumor Research Center of the Department of Neurological Surgery, School of Medicine, University of California, San Francisco, California 94143

Treatment of 9L and 9L-2 cells, which are, respectively, sensitive and resistant to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), with various concentrations of BCNU followed by treatment with 1 mM caffeine potentiated BCNU cytotoxicity by 10-fold with dose modification factors of 1.5 to 1.7. The synergistic effect of caffeine on cellular toxicity diminished when caffeine was added 6 to 24 h after treatment of BCNU. The number of sister chromatid exchanges (SCEs) induced by treatment with BCNU in both cell lines showed a good correlation with cytotoxicity; the number of SCEs induced in 9L cells is 6-fold higher than the number induced in 9L-2 cells. Caffeine potentiated BCNU induction of SCEs in both 9L or 9L-2 cells by the same amount. Caffeine potentiation of BCNU-induced SCEs was also time dependent and was eliminated by a delay of 6 h between BCNU treatment and addition of caffeine. Caffeine had no effect on the formation and removal of DNA cross-links in either 9L or 9L-2 cells after BCNU treatment as determined with the alkaline elution assay. Eighteen to 24 h after BCNU treatment there was an accumulation of 9L cells in late-S-G₂-M phase of the cell cycle which diminished with time. Caffeine treatment potentiated the BCNU-induced accumulation of cells in late-S-G₂-M phase of the cell cycle. Our results suggest that caffeine potentiates BCNU cytotoxicity and induction of SCEs by a mechanism that is independent of repair of alkylation products, but that may depend on alterations of cellular replication in BCNU-treated cells.

¹ Supported in part by NIH Program Project Grant CA-13525 and the Phi Beta Psi Sorority.

² To whom requests for reprints should be addressed, at BTRC, 783 HSW, University of California, San Francisco, CA 94143.

Received 4/29/85. Revised 1/ 2/86. Revised 11/24/86. Revised 5/20/87. Accepted 6/29/87.

This article has been cited by other articles:

				B. Cui, S. P. Johnson, N. Bullock, F. Ali-Osman, D. D. Bigner, and H. S. Friedman Bifunctional DNA Alkylator 1,3-Bis(2-chloroethyl)-1-nitrosourea Activates the ATR-Chk1 Pathway Independently of the Mismatch Repair Pathway Mol. Pharmacol., June 1, 2009; 75(6): 1356 - 1363. [Abstract] [Full Text] [PDF]

				A. J. Janss, A. Maity, C.-B. Tang, R. J. Muschel, W. G. McKenna, L. Sutton, and P. C. Phillips Decreased cyclin B1 expression contributes to G2 delay in human brain tumor cells after treatment with camptothecin Neuro-oncol, January 1, 2001; 3(1): 11 - 21. [Abstract] [PDF]