ALLYL ISOTHIOCYANATE IS SELECTIVELY TOXIC TO TRANSFORMED-CELLS OF THE HUMAN COLORECTAL TUMOR LINE HT29

Allyl isothiocyanate, a constituent of mustard and certain vegetables found in the human diet, was tested for cytotoxic and cytostatic effects in HT29 human colon carcinoma cells in vitro. For an exposure time of 24 h, allyl isothiocyanate exhibited a D(q) of 0.32 mug/ml and a D0 of 0.74 mug/ml. Following detransformation of the cells by treatment with sodium butyrate or dimethylformamide the celts became more resistant to the cytotoxic effects of allyl isothiocyanate, the D(q) increasing to 0.74 mug/ml and the D0 to 0.96 mug/ml (with butyrate) or 0.84 mug/ml (with dimethylformamide). At the D(q) value for detransformed celts the survival of the control cells was reduced to 56%. Allyl isothiocyanate was also found to be less cytostatic to the mass growth of detransformed populations in that daily doses of 1.6 mug/ml over a week reduced the final number of detransformed cells relative to untreated cultures by < 25% whilst growth of the transformed cultures was reduced by > 60%. Given this increased sensitivity of the cells to allyl isothiocyanate when in the transformed state, it is hypothesized that, when consumed in the human diet, this compound may protect against the development of colorectal cancer by selectively inhibiting the growth of transformed cell clones within the gastrointestinal mucosa.