Synthesis of interferon-induced polypeptides in normal and chromosome 21-aneuploid human fibroblasts: relationship to relative sensitivities in antiviral assays.

Localization of the gene for the species specific response to interferon (IFRC) to human chromosome 21 has stimulated interest in the effect of aneuploidy for chromosome 21 on cell sensitivity to interferon. Previous reports have shown that the relative sensitivities of trisomy 21, diploid and monosomy 21 human fibroblasts as measured in an antiviral assay are greater than the ratio 0.67 : 1.0 : 2 predicted on the basis of gene dosage for IFRC. As an alternative test for sensitivity, we have investigated the synthesis of interferon-induced polypeptides visualized by 2-dimensional gel electrophoresis and autoradiography. Of 10 such polypeptides identified, 3 were measured quantitatively in 2 diploid, 2 trisomic, and one monosomic fibroblast strains. In contrast to the antiviral response, the relative responses in this test correspond closely to expected gene dosage relationships over a range of interferon concentrations from 0.5 to 5000 units/ml. These results are compatible with the conclusion that the number of IFRC gene products (presumed to be the interferon receptor) per cell is proportional to the number of IFRC genes. Thus, the amplified effect of aneuploidy as measured in the antiviral response appears to result from some step subsequent to synthesis of interferon receptors and formation of interferon-receptor complexes.