Cytogenetic effects of recombinant interferon-γ on lymphocytes cultures from patients with non–small cell lung cancer

Abstract

Therapeutic effects of human interferons (IFN) on malignancies and infectious diseases have been demonstrated in several clinical trials. The effects of IFN alone or combined with other treatment modalities (radiotherapy and chemotherapy) in lung cancer are under investigation. Experimental data suggest that some cytokines, such as IFN-α and IFN-γ, exhibit cytogenetic properties in human normal lymphocytes from peripheral blood, but the mechanisms are not clear. The aim of the present study was to investigate the in vivo cytotoxic and cytostatic activity of IFN-γ. Patients with certain cases of non–small cell lung cancer not eligible for chemotherapy or chemoradiotherapy were treated with thoracic radiotherapy. After tumor relapse, local treatment with instillations of IFN-γ through the fiberoptic bronchoscope followed. To clarify the cytogenetic activity of IFN-γ, sister chromatid exchange (SCE) and proliferation rate index (PRI) were evaluated in lymphocyte cultures from these patients' peripheral blood samples immediately after diagnosis (baseline), 30 days after radiotherapy, and after the fifth instillation of IFN-γ. Our results show a decrease in SCE frequency and PRI values in lymphocytes after treatment with IFN-γ, suggesting that IFN-γ does not have cytotoxic activity but, in contrast, may induce repair mechanisms, as shown in earlier studies in other biologic models.