Anti-L antibody and cytosine arabinoside acting synergistically produced an inhibition of growth of L cells in vitro. This effect was dependent upon both antibody and cytosine arabinoside concentrations with a 1:200 dilution of antiserum and a 0.10 µg/ml (4 × 10-7 M) concentration of drug being optimal. There was a 50% reduction in the growth rate of such 24-hr cell cultures, and the effect was due primarily to inhibition of cell growth rather than cell lysis. Replicate long-term cell cultures showed that antiserum (IgG fraction) stimulated uptake of 3H-cytosine arabinoside into nuclear DNA of cells. In acute 3H-cytosine arabinoside uptake studies, antibody had no discernable effect upon the transport of drug into the cell but, rather, stimulated an event subsequent to transport, presumably phosphorylation of drug. Indeed, the antibody-enhanced uptake of 3H-cytosine arabinoside appeared first in the total isotope pool of the cells, followed by appearance in the nondiffusible pool, and, finally, in the acid-insoluble pool of cells. Moreover, antibody stimulation of labeled drug into the nondiffusible pool was exquisitely dependent upon energy sources. In total, these observations suggest that antibody stimulated cytosine arabinoside uptake by activation of phosphorylation pathways with subsequent incorporation of the phosphorylated drug into DNA. Enhanced incorporation of drug into nuclear DNA of antibody-treated cells was thus correlated with inhibition of cell replication. Therefore, it is possible to modulate tumor cell replication in vitro by the judicious use of antibody and cytosine arabinoside.

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