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Effect of a Hepatic Activation System on the Antiproliferative Activity of Hexamethylmelamine Against Human Tumor Cell Lines by Krys J. Miller; Renee M. McGovern; Matthew M. Ames is a Medicine article available to read on EtoBox.

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Incubation of hexamethylmelamine for 1 h with human tumor cell lines in culture did not inhibit colony formation at concentrations up to the limit of drug solubility (200 micrograms/ml). When 1-h incubations were carried out in the presence of a 9,000 g rat liver supernatant preparation and an NADPH-generating system, hexamethylmelamine markedly reduced colony formation. Cyclophosphamide inhibition of colony formation was also dependent on the presence of a 9,000 g supernatant preparation and an NADPH-generating system in incubation mixtures. A 1-h incubation of N-methylolpentamethylmelamine (a DNA-alkylating metabolite formed during N-demethylation of hexamethylmelamine) with human tumor cell lines reduced colony formation in the absence of the liver-activating system. Substantial NADPH-dependent N-demethylation of hexamethylmelamine was observed with rat liver, lung, and kidney microsomal preparations. In contrast, little or no HMM metabolism was observed with tumor cells, tumor cell homogenates, or NADPH-fortified tumor cell microsomal preparations. NADPH-dependent formation of cytotoxic metabolites is a prerequisite for antiproliferative activity of hexamethylmelamine against t

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Author

Krys J. Miller; Renee M. McGovern; Matthew M. Ames

Publisher

Springer; Springer-Verlag; Springer Verlag; Springer Science and Business Media LLC (ISSN 0344-5704)

Published

1984

Language

EN

Field

Medicine (Health Sciences)