Distribution, metabolism, and irreversible binding of hexamethylmelamine in mice bearing ovarian carcinoma

✍ Scribed by Enrico Garattini; Tina Colombo; Maria Grazia Donelli; Paolo Catalani; Marina Bianchi; Maurizio D'Incalci; Claudio Pantarotto

• Publisher: Springer
• Year: 1983
• Tongue: English
• Weight: 451 KB
• Volume: 11
• Category: Article
• ISSN: 0344-5704
• DOI: 10.1007/bf00257418

✦ Synopsis

The covalent binding of hexamethylmelamine (HMM) and its metabolites was studied in liver, tumor, blood, kidney, spleen, lung, brain, heart, and small intestine after a single IP injection of 2,4,6-14C-hexamethylmelamine (50 mg/kg) to C57Bl/6J female mice bearing 20-day-old M5076/73A ovarian cancer. Covalent binding to tissue macromolecules was measured 2, 10, and 40 h after injection of the drug. At 2 h liver and small intestine showed the highest levels of irreversibly bound metabolites, the lowest being found in brain and heart. Except in the small intestine, where a decrease was observed between 2 and 10 h, the level of covalent binding was constant up to 40 h. HMM metabolism was also studied. Tissue distribution of pentamethylmelamine (PMM), 2,2,4,6-tetramethylmelamine (TMM), and 2,4,6-trimethylmelamine (TriMM) was determined at the three times considered. At 2 h the drug was already extensively metabolized, TriMM being the major metabolite among those determined.