RT Journal Article
SR Electronic
T1 Treatment of Reuber H35 Hepatoma Cells with Carrier-Bound Methotrexate
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 505
OP 508
VO 19
IS 3
A1 JOHN M. WHITELEY
A1 ZENIA NIMEC
A1 JOHN GALIVAN
YR 1981
UL http://molpharm.aspetjournals.org/content/19/3/505.abstract
AB Methotrexate (MTX), 40 µM, covalently linked to bovine serum albumin (BSA), was ineffective in suppressing the growth of an MTX transport-resistant strain of Reuber hepatoma H35 cells (I50(MTX) ∼ 3.5 µM). However, conjugation of MTX with poly(L-lysine) led to cell growth repression at levels of <0.1 µM. In fact, both the parent H35 line and transport-resistant sublines showed a similar response to treatment with MTX[poly(L-lysine)] (I50 ∼ 70 nM). Depressed cell growth after drug treatment of the H35 cells and the resistant sublines could be partially reversed by treatment with thymidine/hypoxanthine. Additionally, folinic acid was effective for preventing MTX[poly(L-lysine)] toxicity in H35 cells but could not do so for the MTX transport deficient sublines, presumably because of its inability to enter the cells. These data are consistent with the proposal that MTX[poly(L-lysine)] is toxic to both cell lines via a blockade of the one-carbon metabolic pathway.