Effect of galactose on interaction of N-(2-hydroxypropyl)methacrylamide copolymers with hepatoma cells in culture: preliminary application to an anticancer agent, daunomycin.
A series of copolymers were prepared containing 1,2:3,4-di-O-isopropylidene-6-O-methacryloyl-alpha-D-galactopyranose (0 to 99 mol %), methacryoyltyrosinamide and N-(2-hydroxypropyl)methacrylamide (99 to 0 mol %). The effect of galactose content on interaction with hepatoma cells in vitro was studied. Increased galactose content caused increased accumulation of N-(2-hydroxypropyl)methacrylamide copolymers by two human hepatoma cell lines (Hep G2 and SAH), but accumulation by rat and mouse hepatoma (HTC and NCTC) was not galactose dependent. Accumulation of N-(2-hydroxypropyl)methacrylamide copolymers by Hep G2 was shown to be an active process, being inhibited by low temperature and by the metabolic inhibitor 2,4-dinitrophenol. Addition of N-acetylgalactosamine and polymer-galactose to the incubation medium resulted in a concentration-dependent inhibition of accumulation of galactose-containing polymers. Addition of fucose or galactose was without effect at the concentrations used. Polymers bearing galactosamine or fucosylamine residues and, in addition, daunomycin were evaluated for cytotoxicity against Hep G2 and SAH. N-(2-Hydroxypropyl)methacrylamide copolymer-bound daunomycin produced a dose-dependent inhibition of DNA synthesis (measured by incorporation of [3H]thymidine), and the galactose-containing polymer showed greatest inhibition.
O'Hare
K B
KB
Department of Biological Sciences, University of Keele, Staffordshire, United Kingdom.
Hume
I C
IC
Scarlett
L
L
Chytrý
V
V
Kopecková
P
P
Kopecek
J
J
Duncan
R
R
D000178:Acrylamides / Q000378:metabolism*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D003630:Daunorubicin / Q000008:administration & dosage / Q000378:metabolism; D004337:Drug Carriers; D005690:Galactose / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D051379:Mice; D011108:Polymers; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000378:metabolism
D000178:Acrylamides; D004337:Drug Carriers; D011108:Polymers; C032976:N-(2-hydroxypropyl)methacrylamide; D005690:Galactose; D003630:Daunorubicin