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Molecular Pharmacology, Vol 14, 210-214, Copyright © 1978 by the American Society for Pharmacology and Experimental Therapeutics

Synthesis of Methotrexate Polyglutamates in Cultured Human Cells

D. S. ROSENBLATT 1, V. M. WHITEHEAD 1, M. M. DUPONT 1, M.-J. VUCHICH 1, and N. VERA 1

1 Medical Research Council Genetics Group, McGill University-Montreal Children's Hospital; Research Institute, Montreal General Hospital; and Departments of Pediatrics and Medicine, McGill University, Montreal, Quebec, Canada H3H 1P3

We describe the biosynthesis of po1y-ggr-glutamyl metabolites of methotrexate in cultured human fibroblasts. The accumulation of polyglutamates by these cells is dependent on the concentration of methotrexate in the culture medium, duration of incubation, and stage of the culture cycle. When [3H]methotrexate is replaced with equimolar unlabeled methotrexate, label is found in successively longer polyglutamates. Synthesis of the polyglutamates is dependent on the continued presence of methotrexate in the culture medium.

Submitted on June 1, 1977
Accepted on September 13, 1977




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