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 propert ies potentially useful to man. As its genotoxic capacity has been poor ly evaluated, in this investigation we determined its effect on the pr oduction of sister-chromatid exchanges (SCEs), and on the level of mit otic index (MI) in cultured human lymphocytes and in mouse bone marrow cells in vivo. The proliferative index (PI), and the average generati on time (AGT) were also determined for human lymphocytes and in mouse bone marrow cells respectively. The in vitro study was made in two don ors using NDGA doses of 1.1, 3.6, 6.7, 13.5, and 27.0 mu M; and for th e 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 lymphocy tes 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 P I a decrement of more than 50% and a cell cycle delay was detected onl y with the high dose. In the study with bone marrow cells, a statistic ally 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 leve l), The MI decreased only with the high dose and no modification was o bserved with respect to AGT. In conclusion, in both used models the st udy demonstrated that NDGA produced genotoxic and cytotoxic effects. ( C) 1998 Elsevier Science B.V.