[(IgG)2 protein A]2 complex stimulates cytosine arabinoside incorporation into DNA and inhibits L cell proliferation.
A Mr = 716 000 complex, [(IgG)2 Protein A]2, formed when Protein A is mixed with a molar excess of IgG anti-L cell antibody, augmented [3H]thymidine incorporation in DNA and growth of a murine transformed L cell line. It was also possible to augment the incorporation of [3H]cytosine arabinoside (2.3-fold) in DNA by the binding of this complex to L cells. A synergistic inhibition of L cell proliferation was produced using the complex and certain concentrations of cytosine arabinoside. By binding the complex to L cells, a 5-fold lower concentration of cytosine arabinoside (0.050 microgram/ml) was as effective in inhibiting cell replication as the higher dose of the drug (0.25 microgram/ml) with cells bound by IgG antibody alone, and a 20-fold lower concentration compared to the effects of the drug itself (1.0 microgram/ml). Addition of 10 microM thymidine to the complex permitted the use of an even lower dose of cytosine arabinoside (0.004 microgram/ml) for inhibition of cell growth. Thymidine caused this effect by producing an even greater incorporation of drug into the DNA of complex-stimulated cells. Thus, by stimulating the cell with the immune [(IgG)2 Protein A]2 complex it was possible to stimulate uptake of a chemotherapeutic nucleoside and selectively inhibit cell replication at non-toxic doses of nucleoside.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003561:Cytarabine / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis*; D004357:Drug Synergism; D006131:Growth Inhibitors / Q000494:pharmacology*; D007106:Immune Sera / Q000494:pharmacology; D007074:Immunoglobulin G; D007739:L Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D011817:Rabbits; D013205:Staphylococcal Protein A / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D006131:Growth Inhibitors; D007106:Immune Sera; D007074:Immunoglobulin G; D013205:Staphylococcal Protein A; D003561:Cytarabine; D004247:DNA; D013936:Thymidine