IN-VIVO AND IN-VITRO ANTIGENOTOXIC EFFECT OF NORDIHYDROGUAIARETIC ACID AGAINST SCES INDUCED BY METHYL METHANESULFONATE

Nordihydroguaiaretic acid (NDGA) is a phenolic lignan which has shown to cause a variety of actions potentially useful for human health; the refore, in this investigation we determined its capacity for inhibitin g the rate of sister chromatid exchanges (SCEs) induced by methyl meth anesulfonate (MMS). We tested the effect of 0.25, 0.50, 1.0, and 2.0 m u M of NDGA on the damage exerted by 55 mu M of MMS. Cultured human ly mphocytes from two female donors were used for the experiment. The bes t result concerning its modulatory action was obtained with 1.0 mu M o f NDGA; with this dose the mean inhibitory index including both donors reached 68.2%. The values obtained for the mitotic and proliferative indexes were not significantly modified with respect to the basal data . We also used the mouse bone marrow in vivo system to evaluate the in hibitory effect of the chemical. In this study we tested 1.0, 6.0, and 11.0 mg/kg of NDGA intraperitoneally (i.p.) administered 1 h before a n i.p. injection of MMS (40 mg/kg). The best inhibitory index in this model corresponded to the dose of 11 mg/kg of NDGA (86.9%). The mitoti c index and the average generation time showed no significant variatio n with respect to the control data. Our study established that NDGA pr oduces antigenotoxic action in mammalian cells in vitro and in vivo. ( C) 1998 Elsevier Science B.V. All rights reserved.