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; therefore, in this investigation we determined its capacity for inhibiting the rate of sister chromatid exchanges (SCEs) induced by methyl methanesulfonate (MMS). We tested the effect of 0.25, 0.50, 1.0, and 2.0 mu M of NDGA on the damage exerted by 55 mu M of MMS. Cultured human lymphocytes from two female donors were used for the experiment. The best result concerning its modulatory action was obtained with 1.0 mu M of 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 inhibitory 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 an 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 mitotic index and the average generation time showed no significant variation with respect to the control data. Our study established that NDGA produces antigenotoxic action in mammalian cells in vitro and in vivo. (C) 1998 Elsevier Science B.V. All rights reserved.