Skip to main content
OSTI.GOVU.S. Department of Energy Office of Scientific and Technical Information
U.S. Department of Energy
Office of Scientific and Technical Information
 

Studies of formation and efflux of methotrexate polyglutamates with cultured hepatic cells

Journal Article · · Adv. Exp. Med. Biol.; (United States)
;
Methotrexate polyglutamates are extensively synthesized when cultured hepatocytes and H35 hepatoma cells are exposed to micromolar concentrations of methotrexate. The predominant species found within the cell have from two to four additional gamma-linked glutamate residues. When either cell type containing a mixture of methotrexate and its polyglutamate derivatives is exposed to medium lacking methotrexate, there is a rapid release of methotrexate. This release has a T/sub 1/2/ of 2 to 4 min and is apparently complete within 30 to 60 min. Methotrexate polyglutamates leave the cells much more slowly and appear to do so by two mechanisms. Although cleavage to methotrexate and subsequent efflux appears to be quantitatively the more important pathway, there is also a slow, finite loss of intact methotrexate polyglutamates from cells which exclude trypan blue. The T/sub 1/2/ for the loss of methotrexate polyglutamates by both cell types, when placed in medium lacking methotrexate, is approximately 6 to 8 hr. These results suggest that the polyglutamate derivatives are forms of methotrexate which are as cytotoxic as methotrexate but which offer a potentially greater capacity for cellular destruction because they are retained longer in the tissue.
Research Organization:
Division of Laboratories and Research, New York State Department of Health, Albany
OSTI ID:
5590463
Journal Information:
Adv. Exp. Med. Biol.; (United States), Journal Name: Adv. Exp. Med. Biol.; (United States) Vol. 163; ISSN AEMBA
Country of Publication:
United States
Language:
English

Similar Records

Characteristics of the accumulation of methotrexate polyglutamate derivatives in Ehrlich ascites tumor cells and isolated rat hepatocytes
Journal Article · Fri Dec 31 23:00:00 EST 1982 · Adv. Exp. Med. Biol.; (United States) · OSTI ID:5590470
Regulatory aspects of the glutamylation of methotrexate in cultured hepatoma cells
Journal Article · Sat Oct 15 00:00:00 EDT 1983 · Arch. Biochem. Biophys.; (United States) · OSTI ID:5099165
Soman and glutamate toxicity in cultured cortical and hippocampal neurons: An in vitro model for testing neuroprotective drugs
Technical Report · Thu May 13 00:00:00 EDT 1993 · OSTI ID:7300607

Related Subjects

550200* -- Biochemistry
560305 -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMIDES
AMINO ACIDS
ANTIMETABOLITES
BIOCHEMICAL REACTION KINETICS
BODY
CARBOXYLIC ACIDS
CELL CULTURES
DIGESTIVE SYSTEM
DISEASES
DRUGS
GLANDS
GLUTAMINE
HEPATOMAS
KINETICS
LIVER
MEMBRANE TRANSPORT
METABOLITES
METHOTREXATE
NEOPLASMS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
REACTION KINETICS