FIELD BEAN PROTEASE INHIBITOR MITIGATES THE SISTER-CHROMATID EXCHANGES INDUCED BY BROMOFORM AND DEPRESSES THE SPONTANEOUS SISTER-CHROMATID EXCHANGE FREQUENCY OF HUMAN-LYMPHOCYTES IN-VITRO

The mutagenicity of a trihalomethane-bromoform (CHBr3)-was assessed by the in vitro sister-chromatid exchange (SCE) assay using human periph eral blood lymphocytes. CHBr3 was found to induce SCEs significantly i n a dose-dependent manner. When the cells were exposed to 600 ng CHBr3 /ml of the medium, the SCE/cell mean reached a value as high as 18.78 +/- 0.17. Beyond this concentration, CHBr3 proved to be cytotoxic. A p rotease inhibitor (PI), purified appreciably by affinity chromatograph y from fieldbean (FB), was able to suppress significantly in a dose-de pendent way the high SCE frequencies induced by this specific concentr ation of CHBr3 (600 ng/ml). Addition of 600 mu g of FBPI/ml of the med ium brought down the CHBr3-induced high SCEs to near (8.80 +/- 0.15) b ase line or control value (8.45 +/- 0.21). A study of the effect of FB PI on the normal low SCE frequencies in these cells indicated that the FBPI has the intrinsic property to suppress in a dose-dependent manne r these SCEs in the lymphocytes. This functional property of FBPI, whi ch is related to its protease inhibitory activity and which is destroy ed when it is inactivated by autoclaving, makes it an effective antimu tagenic/chemopreventive agent.