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Sublines of murine leukemia L1210 cells were selected for resistance to the inhibitory effect of interferon on cell division. These cells were also resistant to the antiviral effect of interferon. The character of interferon resistance was stable and mitotically perpetuated in the ab sence of interferon. Using a technique developed to detect the presence of small numbers of interferon-resistant cells, we found that 0.004-1% of the cells of wild or cloned populations of sensitive cells were interferon resistant. Cultivation of the interferon-sensitive cell population with interferon resulted in the exponential increase and ultimate selection of a population of interferon-resistant cells. Fluctuation analysis tests indicated that interferonresistant variants originated by spontaneous random change rather than by induction by interferon. Interferon could be recovered from extracts of interferon-treated interferon- sensitive L1210 cells, but not from interferontreated, interferon-resistant cells.
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Gresser et al. (1974) studied this question.
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