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Metabolic activation of hexamethylmelamine and pentamethylmelamine by liver microsomal preparations

Metabolic activation of hexamethylmelamine and pentamethylmelamine by liver microsomal preparations

Life Sciences 29(15): 1591-1598

Incubation of [14C]-ring labeled hexamethylmelamine [HMM] and pentamethylmelamine [PMM] [antitumor agents] with rat and mouse liver microsomal preparations results in metabolic activation of the 2 drugs as measured by covalent binding of radiolabel to acid-precipitable microsomal macromolecules. Covalent binding is dependent on viable microsomes, NADPH and molecular O2. Binding of HMM (280 pmol/mg protein per 15 min) was .apprx. 5 times greater than that observed for PMM (60 pmol/mg protein per 15 min) and represents 0.22% of incubated material. Similar results were found with [14C]-methyl labeled substrates. Pretreatment with phenobarbital increased covalent binding while addition of SKF 525-A, addition of glutathione or incubation in an 80% CO atmosphere reduced covalent binding.

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Accession: 005879736

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PMID: 6795407

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