This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Hirst, D. G. Articles by Hazlehurst, J. L. Search for Related Content PubMed PubMed Citation Articles by Hirst, D. G. Articles by Hazlehurst, J. L.

Effect of Partition Coefficient on the Ability of Nitroimidazoles to Enhance the Cytotoxicity of 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea¹

Department of Radiology, Stanford University School of Medicine, Stanford, California 94305

The ability of three nitroimidazoles [SR-2508, misonidazole (MISO), and benznidazole] with differing octanol-water partition coefficients to enhance the cytotoxicity of the nitrosourea 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was evaluated in two mouse tumors (the KHT sarcoma and the SCC VII/St carcinoma). These results were compared with the effect on two normal tissues (bone marrow CFU-S and testis spermatogonia).

When given as a large single dose, benznidazole was more effective than MISO in enhancing the cytotoxicity of CCNU to both tumors. SR-2508 had no effect. The advantage of benznidazole over MISO was lost, however, because benznidazole gave more toxicity in the normal tissues than MISO.

In experiments where the nitroimidazoles were administered by multiple small injections to maintain a blood plasma level between 50 and 100 µg/ml, benznidazole was also more effective than MISO in enhancing CCNU cytotoxicity in the tumors. In each case, enhancement was rather less than that obtained with large single injections. Again, however, benznidazole did not produce a consistently greater therapeutic gain than MISO because it also enhanced normal tissue toxicity while MISO did not. SR-2508 was ineffective in both tumors and normal tissues.

We conclude that neither SR-2508 nor benznidazole are superior to MISO in combination with CCNU.

¹ This work was supported by Grants CA-15201 and CA-25990 from the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed.

Received 6/30/82. Accepted 1/14/83.

This article has been cited by other articles:

				B. G. Wouters, Y. M. Delahoussaye, J. W. Evans, G. W. Birrell, M. J. Dorie, J. Wang, D. MacDermed, R. K. Chiu, and J. M. Brown Mitochondrial Dysfunction after Aerobic Exposure to the Hypoxic Cytotoxin Tirapazamine Cancer Res., January 1, 2001; 61(1): 145 - 152. [Abstract] [Full Text]