Differential response to 1,3-bis (2-chloroethyl)-1-nitrosourea in drug-resistant and -sensitive 9L rat brain tumor cells pretreated with α-difluoromethylornithine and 6-thioguanine

Karl J. Hunter

Brain Tumor Research Center of the Department of Neurological Surgery, and the Departments of Radiation Oncology and Laboratory Medicine, School of Medicine, University of California, San Francisco, CA 94143, USA

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Dennis F. Deen,

Dennis F. Deen

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Laurence J. Marton,

Corresponding Author

Laurence J. Marton

The Editonal Office, 1360 Ninth Avenue, Suite 210, San Francisco, CA 94122, USASearch for more papers by this author

Karl J. Hunter,

Karl J. Hunter

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Dennis F. Deen,

Dennis F. Deen

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Laurence J. Marton,

Corresponding Author

Laurence J. Marton

The Editonal Office, 1360 Ninth Avenue, Suite 210, San Francisco, CA 94122, USASearch for more papers by this author

First published: 15 October 1989

https://doi.org/10.1002/ijc.2910440417

Citations: 16

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Abstract

Pretreatment of 9L cells with either α-difluoromethylorni-thine (DFMO), which depletes intracellular levels of poly-amines, or 6-thioguanine (6TG), which substitutes for guanine in DNA, potentiates the cytotoxic effects of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU). We examined the effects of these 2 agents in combination on the cytotoxicity of BCNU in sensitive (9L) and resistant (BTRC-19) rat brain tumor cell lines. 9L cells were incubated with 0.2 μM 6TG for 72 hr; during the last 48 hr, I mM DFMO was added to cell cultures. The cytotoxicity of BCNU in pretreated cells was increased in an additive manner compared with the effects of each agent alone. Results of experiments in which the BCNU-resistant BTRC-19 cell line was treated similarly showed that only 6TG enhanced BCNU cytotoxicity. Flow cytometry studies showed that these effects are not related to cell-cycle processes.

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Volume44, Issue4

15 October 1989

Pages 658-660

Differential response to 1,3-bis (2-chloroethyl)-1-nitrosourea in drug-resistant and -sensitive 9L rat brain tumor cells pretreated with α-difluoromethylornithine and 6-thioguanine

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Differential response to 1,3-bis (2-chloroethyl)-1-nitrosourea in drug-resistant and -sensitive 9L rat brain tumor cells pretreated with α-difluoromethylornithine and 6-thioguanine

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