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Differential Potentiation of 1,3-Bis(2-chloroethyl)-1-nitrosourea by -Difluoromethylornithine in Chloroethylnitrosourea-sensitive and -resistant 9L Rat Brain Tumor Cells in Vitro¹

Brain Tumor Research Center of the Department of Neurological Surgery [S. M. O., P. J. T., B. G. F., D. F. D., M. L. R., L. J. M.], the Department of Radiation Oncology [D. F. D.], and the Department of Laboratory Medicine [L. J. M.], School of Medicine, University of California, San Francisco, California 94143

-Difluoromethylornithine, an enzyme-activated, irreversible inhibitor of ornithine decarboxylase, inhibited the growth of both chloroethylnitrosourea-sensitive and -resistant 9L rat brain tumor cells in vitro. After 48 hr of treatment with 10 mM -difluoromethylornithine, the putrescine and spermidine contents of both resistant and sensitive cells were less than 5% of control levels, but the spermine level was slightly elevated. The cytotoxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea, as measured by a colonyforming efficiency assay, was significantly increased in -difluoromethylornithine-pretreated sensitive cells but not in resistant cells treated with this polyamine inhibitor. With the sister chromatid exchange assay, we found that -difluoromethylornithine pretreatment increased 1,3-bis(2-chloroethyl)-1-nitrosourea-induced damage to chromosomes in sensitive but not in resistant cells.

¹ Supported by American Cancer Society Grant RD-137, NIH Grant CA-13525, and the Morris Stulsaft Foundation.

² Recipient of travel grants from The Swedish Natural Science Research Council (R-RA 4685-100) and The Swedish Medical Research Council (B 81-04R-6065-504106065).

³ Recipient of an Aaron Silvera Fellowship; supported by NIH Training Grant CA-09215.

⁴ Recipient of Teacher Investigator Development Award NIH-1K07-NS00604 from National Institute of Neurological and Communicative Disorders and Stroke.

⁵ To whom requests for reprints should be addressed, at Department of Laboratory Medicine, N-531, University of California, San Francisco, Calif. 94143.

Received 4/19/82. Accepted 4/21/83.

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