[(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.