DIFFERENTIAL ACTION ON CANCER AND NORMAL TISSUE BY ADRENOCHROME MONOAMINOGUANIDINE METHANESULFONATE AND CYTOCHROME-C COMBINED WITH RADIOTHERAPY

Purpose: The possibility that radioprotective effects on potent natura l killer (NK) cells by adrenochrome monoaminoguanidine methanesulfonat e + cytochrome C during radiotherapy (RT) for lung cancer might result in the radiosensitization of human lung cancer cells in vivo is exami ned. Methods and Materials: Human lung cancer xenografts in the right hind legs of KSN mice (10 weeks old) were locally irradiated with 20 G y of X ray. Adrenochrome monoaminogluanidine methanesulfonate (AMM) (1 0 mg/kg/day) and/or cytochrome C (CCC) (5 mg/kg/day) were given intrap eritoneally immediately before or after RT, followed by daily administ ration for 4 days. Natural killer activities of host splenocytes were also tested with the standard Cr-51 releasing assay with YAC-1 cells a s target cells. In a clinical study, 65 patients with lung cancer were treated with more than 50 Gy of RT with or without combination with A MM + CCC, OK-432 or AMM + CCC + OK-432. Before and after RT, lymphocyt e subsets in the peripheral blood were examined with dichromatic analy sis using an Ortho Spectrum IIIFCM system and fluorescent MABs In this study, the change in the absolute number of each subset was investiga ted. Results: Adrenochrome monoaminoguanidine methanesulfonate + cytoc hrome C augumented NK activity in KSN nude mice, protected potent NK c ells in patients with lung cancer against RT and sensitized the human lung cancer xenografts to RT.Conclusion: Adrenochrome monoaminoguanidi ne methanesulfonate + cytochrome C may have the potential as a differe ntial modulator of radiosensitivity of normal tissues and of tumors.