Antigenotoxic Effects of Thymoquinone against Benzo[a]Pyrene and Mitomycin C -Induced Genotoxicity in Cultured Human Lymphocytes

Thymoquinone (TQ) is the main active ingredient extracted from the black seed (Nigella sativa L.) Previous work on the antigenotoxic properties of TQ in animal cell systems has yielded inconsistent results. We investigated the antigenotoxic effect of different concentrations of TQ in human lymphocyte cultures challenged with two standard mutagens: benzo[a]pyrene (B[a]P; 16 μM), and mitomycin C (MMC; 1 μM). TQ dose-dependently decreased the activities of B[a]P and MMC in three short-term genotoxicity tests: the sister chromatid exchange (SCE), the cytokinesis-blocked micronucleus (CBMN) assay and 6-thioguanine resistance (TGr) test. Also, TQ lowered the level of free radicals generated by cultured human granulocytes alone and in the presence of both B[a]P and the granulocyte activator phorbol myristate acetate (PMA). These results confirm a significant dose-dependent antigenotoxic action of TQ on direct and indirect acting mutagens in vitro, and suggest that inhibition of free radical pathways could play an important role in this action. The genoprotective potential of TQ remains to be evaluated at the clinical level as the combination of TQ with some anti-cancer drugs can reduce chemotherapy-induced DNA damage of the non-tumor tissues.