/V-Demethylation of the Antineoplastic Agent Hexamethylmelamine by Rats and Man1

National Cancer Institute, USPHS. Presented in part at the 62nd Annual Meeting of the American Association for Cancer Research, Inc., Chicago. 111..April 1971 (37). 2Career Development Awardee of the National Cancer Institute (IK4-CA-8245-05). 3The abbreviations used are: HMM, hexamethylmelamine [2,4,6tris(dimethylamino)-i-lriazine] (NSC-13875); TEM, triethylenemelamine [2,4,6-tris(l-aziridinyl)-i-triazine]; DEGS, diethylene glycol succinate; N BP, 4-(p-nitrobenzyl)pyridine. Received April 27, 1973; accepted August 6, 1973. similar s-triazine compounds, TEM and trimethylolmelamine [2,4,6-tris(methylolamino)-i-triazine] (12, 20, 21). Clinical trials with HMM were initiated by Wilson and de la Garza (36) and by Louis et al. (24). Phase II studies with HMM were conducted, and the response rate of pa tients demonstrated HMM to be worthy of further clini cal study especially for lung carcinoma. The clinical literature for HMM has been recently reviewed by Blum et al. (8). Although HMM has been used in several clinical trials with cancer patients, information concerning the mech anism of action of this drug and its metabolism is sparse. Studies in our laboratory with HMM have included the development of an ion-exchange method for the isolation and quantitation of HMM (10) and an investigation of the plasma and urinary levels of HMM and its metabolites in treated cancer patients (11). This paper describes the metabolism of HMM-methyl-14C and reports the identi