Establishment of new interferon-gamma-resistant mutant cells with dominant phenotypes

We established interferon-gamma-resistant (IGR) cells from a human colon adenocarcinoma cell line, LoVo. Their resistance was extremely high, and the ED50 values of IFN-gamma were > 10(5) IU/ml. Interestingly, although IGR-5 cells were still sensitive to the antiproliferative effect of IFN-alpha, the cells lost responsiveness to the antiviral effects of both IFN-alpha and gamma. Another clone, IGR-53, was unresponsive to both the antiproliferative and antiviral effects of either IFN-alpha or gamma. Furthermore, the IFN-gamma-resistant phenotypes of IGR cells were apparently dominant to the parental LoVo cells based on complementation tests. Although IGR-53 cells lack IFN-gamma receptors, IGR-5 cells seemed to have functional IFN-gamma receptors and processing mechanisms of IFN-gamma bound to the receptors. Northern analysis showed that IGR-5 cells responded to IFN-gamma and alpha, but the enhancement of IRF-1 expression by IFN-gamma was markedly suppressed.