+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 005879736

Download citation: RISBibTeXText

PMID: 6795407


Related references

Mutagen screening by a simplified bacterial fluctuation test use of microsomal preparations and whole liver cells for metabolic activation. Mutation Research 48(3-4): 287-294, 1977

Hexamethylmelamine and pentamethylmelamine: an update. Drug Intelligence and Clinical Pharmacy 17(6): 418-424, 1983

Routes of elimination of hexamethylmelamine and pentamethylmelamine in the rat. Xenobiotica; the Fate of Foreign Compounds in Biological Systems 12(5): 315-321, 1982

Pharmacokinetics of hexamethylmelamine and pentamethylmelamine in mice. Cancer Treatment Reports 65(7-8): 669-672, 1981

Pentamethylmelamine: review of an aqueous analog of hexamethylmelamine. Cancer Treatment Reports 70(3): 383-389, 1986

Activation of benzo[a]pyrene and aflatoxin B1 to mutagenic chemical species by microsomal preparations from rat liver and small intestine in relation to microsomal epoxide hydrolase. Mutagenesis 1(1): 45-48, 1986

Disposition and metabolism of pentamethylmelamine and hexamethylmelamine in rabbits and humans. Cancer Research 39(12): 5016-5021, 1979

Uptake and metabolism of hexamethylmelamine and pentamethylmelamine by L5178Y lymphoblasts in vitro. Cancer Research 40(12): 4489-4494, 1980

Randomized phase II trial of hexamethylmelamine versus pentamethylmelamine in carcinoma of the bilharzial bladder. Cancer Treatment Reports 68(5): 793-794, 1984

Hexamethylmelamine and pentamethylmelamine tissue distribution in M5076/73A ovarian cancer-bearing mice. Cancer Treatment Reports 66(1): 127-133, 1982

Metabolic inactivation of 8-methoxypsoralen (8-MOP) by rat-liver microsomal preparations. Mutation Research 79(4): 327-330, 1980

Absorption and metabolism of hexamethylmelamine and pentamethylmelamine in rat everted perfused gut segments: correlation with in-vivo data. Journal of Pharmacy and Pharmacology 37(9): 629-636, 1985

Metabolic N-oxidation of atropine, hyoscine and the corresponding nor-alkaloids by guinea-pig liver microsomal preparations. Journal of Pharmacy and Pharmacology 28(9): 687-691, 1976

Metabolic activation of the serotonergic neurotoxin para-chloroamphetamine to chemically reactive intermediates by hepatic and brain microsomal preparations. Biochemical Pharmacology 35(10): 1737-1742, 1986

Predicting the oral bioavailability of 19-nortestosterone progestins in vivo from their metabolic stability in human liver microsomal preparations in vitro. Drug Metabolism and Disposition: the Biological Fate of Chemicals 26(11): 1120-1127, 1998