Immunosuppressant deoxyspergualin-induced inhibition of cell proliferationis accompanied with an enhanced reduction of tetrazolium salt

Deoxyspergualin (DSG) has both antitumor and immunosuppressive activities. We explored the mechanism of DSG activities using an aqueous soluble analog ue, methyldeoxyspergualin (MeDSG) for in vitro culture studies. It is known that DSG has inhibitory effects on cell proliferation, and we also observe d that MeDSG inhibited [H-3]-thymidine incorporation by rapidly dividing mu rine T cell hybridomas. However, when tetrazolium (MTT) colorimetric assay was adopted to evaluate its inhibitory effects on cell proliferation, MeDSG induced an enhanced MTT reduction. When we examined whether these results were applicable to the actively dividing cells of other origins than T cell s, similar effects were seen with Raji cells, J774.1 cells and NIH3T3 cells . N-30, another analogue which was capable of suppressing anti-SRBC antibod y production in vivo, also induced inhibition of cell growth and an enhance d MTT reduction. In contrast, the analogue which failed to prevent the anti body production, neither enhanced MTT reduction nor inhibited cell prolifer ation. Our results demonstrated that the ability to generate MTT formazan i n dividing cells is a common property among DSG analogue with the immunosup pressive and antiproliferative activities.