Micronucleus formation and induction of apoptosis by different isothiocyanates and a mixture of isothiocyanates in human lymphocyte cultures

Isothiocyanates (ITCs) are the main sulfur-containing metabolites found in cruciferous vegetables. There is evidence that some ITCs may act as chemopreventive agents against different tumor types and induce apoptosis and modulate cell-cycle progression of highly proliferative cancer cells. However, there are also studies reporting genotoxic or co-carcinogenic effects for some ITCs, such as benzyl ITC and phenyl ITC. Since selectivity for transformed cells and absence of genotoxicity for healthy cells are important pre-requisites for new chernopreventive agents, we investigated micronucleus formation and induction of apoptosis by 4-(methylthio)butylisothiocyanate (MTBITC), sulforaphane and a mixture of ITCs in human T-lymphocyte cultures. We demonstrate that MTBITC sulforaphane and the mixture of ITCs did not induce micronuclei. Moreover, sulforaphane induced a dose-dependent increase in the number of apoptotic, cells, which was significant at the highest concentration tested (30 mu M) (41% versus 18% in the untreated samples, P < 0.05). The mixture of ITCs presented a trend similar to that found for sulforaphane. In fact, the mixture of ITCs was able to induce a dose-dependent increase in the percentage of apoptotic cells, which reached a maximum value at the concentration of 13 mu g/ml (46% versus 19% in control samples, P < 0.05). Induction of apoptosis was not observed in cultures treated with MTBITC. Our results suggest that different ITCs can have different effects. Moreover, although the mixture of lucosinolates (GLs) used in the present study does not reflect the exact composition of broccoli, our findings demonstrate that the quantitative effects of a single, specific ITC can be significantly different from those of an ITC mixture, where other ITCs of the mixture contribute to the outcome observed. (c) 2004 Elsevier B.V. All rights reserved.