In vivo and in vitro induction of sister-chromatid exchanges by nordihydroguaiaretic acid

Nordihydroguaiaretic acid (NDGA) is a phenolic lignan previously used as an antioxidant in commercial products, and with a number of properties potentially useful to man. As its genotoxic capacity has been poorly evaluated, in this investigation we determined its effect on the production of sister-chromatid exchanges (SCEs), and on the level of mitotic index (MI) in cultured human lymphocytes and in mouse bone marrow cells in vivo. The proliferative index (PI), and the average generation time (AGT) were also determined for human lymphocytes and in mouse bone marrow cells respectively. The in vitro study was made in two donors using NDGA doses of 1.1, 3.6, 6.7, 13.5, and 27.0 μM; and for the in vivo study the tested doses were 8.8, 17.6, 35.3, and 70.7 mg/kg of body weight. The results concerning SCE induction in human lymphocytes showed a dose-dependent response with a maximum mean increase of 5.52 SCE in relation to the control level, and with respect to MI and PI a decrement of more than 50% and a cell cycle delay was detected only with the high dose. In the study with bone marrow cells, a statistically significant difference was determined with the high two doses (an increase of 1.06 SCEs with 70.7 mg/kg in relation to the control level). The MI decreased only with the high dose and no modification was observed with respect to AGT. In conclusion, in both used models the study demonstrated that NDGA produced genotoxic and cytotoxic effects.