Radiosensitization of Hypoxic HeLa S3 Cells in Vitro by a New Type of Radiosensitizer: Spermine and Spermidine Amides with Nitro Groups

Summary

A new type of hypoxic cell sensitizer (FNT-series compounds) has been developed and tested on HeLa S3 cells. They have two nitrobenzoyl groups at both ends of the spermine or spermidine in their chemical structures. Their ability to sensitize hypoxic cells is greater than that of misonidazole. Among them, N¹,N¹⁰-bis (4-nitrobenzoyl)-spermidine (FNT-1) was most effective. 1 mM FNT-1 gave a corrected enhancement ratio of 1·71 compared to 1·32 for the same concentration of misonidazole. Its electron affinity, in terms of the half-wave reduction potential, was −350 mV and higher than that of misonidazole (−395 mV). These FNT-series compounds are thought to interact with DNA in two ways; noncovalent linkage between the basic groups of the polyamine and highly acidic phosphate moieties of the nucleic acid and, secondly, the insertion of the nitrobenzoyl groups between base pairs of the DNA double helix. Since spermine and spermidine themselves did not show any sensitizing acitivities, it is suggested that the nitrobenzoyl groups which are introduced in spermine and spermidine, play an important role in sensitization.