ESTABLISHMENT OF NEW INTERFERON-GAMMA-RESISTANT MUTANT-CELLS WITH DOMINANT PHENOTYPES

We established interferon-gamma-resistant (IGR) cells from a human col on adenocarcinoma cell line, LoVo. Their resistance was extremely high , and the ED(50) values of IFN-gamma were >10(5) IU/ml. Interestingly, although IGR-5 cells were still sensitive to the antiproliferative ef fect of IFN-alpha, the cells lost responsiveness to the antiviral effe cts of both IFN-alpha and gamma. Another clone, IGR-53, was unresponsi ve to both the antiproliferative and antiviral effects of either IFN-a lpha or gamma. Furthermore, the IFN-gamma-resistant phenotypes of IGR cells were apparently dominant to the parental LoVo cells based on com plementation tests, Although IGR-53 cells lack IFN-gamma receptors, IG R-5 cells seemed to have functional IFN-gamma receptors and processing mechanisms of IFN-gamma bound to the receptors. Northern analysis sho wed that IGR-5 cells responded to IFN-gamma and alpha, but the enhance ment of IRF-1 expression by IFN-gamma was markedly suppressed.