Effect of sulforaphane on micronucleus induction in cultured human lymphocytes by four different mutagens.
Isothiocyanates (ITCs) are commonly found in cruciferous vegetables. A variety of biological activities have been ascribed to ITCs, such as inhibition of cytochrome P450 enzymes and induction of phase II enzymes in animal models. ITCs are also able to block cell-cycle progression and induce apoptosis in human cancer cells in vitro. In this study, we evaluated the ability of the ITC sulforaphane to protect cultured human lymphocytes from micronucleus (MN) induction by four different mutagens: ethyl methanesulfonate (EMS), vincristrine (VIN), H(2)O(2) and mitomycin C (MMC). To understand the mechanisms of action of sulforaphane, the cultures were treated with the compound before, during and after treatment with the mutagens; in addition, the cultures were evaluated for the induction of apoptosis. Up to 10 microM, sulforaphane was non-genotoxic by itself, while 30 microM sulforaphane reduced the replicative index of the cells by more than 60%. Moreover, 1-10 microM sulforaphane reduced the MN frequency induced by EMS, VIN, H(2)O(2) and MMC in at least one of the treatment protocols; it had no effect on H(2)O(2)-MN induction in the post-treatment protocol, and it increased MN induction by MMC in the pre-treatment protocol. Apoptosis was produced in the cultures treated with sulforaphane alone. The fraction of apoptotic cells was increased after co- or post-treatment with sulforaphane and EMS and MMC, suggesting that sulforaphane-mediated apoptosis may remove highly damaged cells induced by these agents. Other mechanisms are involved in the anti-genotoxic activity of sulforaphane against VIN and H(2)O(2). Taken together, our findings indicate that under certain conditions sulforaphane possesses anti-genotoxic activity in vitro and that further studies are warranted to characterize this property in vivo.
Fimognari
Carmela
C
Department of Pharmacology, University of Bologna, Bologna, Italy. carmela.fimognari@unibo.it
Berti
Fausto
F
Cantelli-Forti
Giorgio
G
Hrelia
Patrizia
P
D016588:Anticarcinogenic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D017879:Isothiocyanates; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced*; D015162:Micronucleus Tests; D016685:Mitomycin / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D010716:Phosphatidylinositols / Q000633:toxicity; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D009153:Mutagens; D010716:Phosphatidylinositols; D013454:Sulfoxides; D013861:Thiocyanates; D016685:Mitomycin; D005020:Ethyl Methanesulfonate; D006861:Hydrogen Peroxide; C016766:sulforaphane