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

Allyl isothiocyanate, a constituent of mustard and certain vegetables found in the human diet, was tested for cytotoxic and cytostatic effec ts 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 resist ant to the cytotoxic effects of allyl isothiocyanate, the D(q) increas ing to 0.74 mug/ml and the D0 to 0.96 mug/ml (with butyrate) or 0.84 m ug/ml (with dimethylformamide). At the D(q) value for detransformed ce lts the survival of the control cells was reduced to 56%. Allyl isothi ocyanate was also found to be less cytostatic to the mass growth of de transformed 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 reduce d by > 60%. Given this increased sensitivity of the cells to allyl iso thiocyanate when in the transformed state, it is hypothesized that, wh en consumed in the human diet, this compound may protect against the d evelopment of colorectal cancer by selectively inhibiting the growth o f transformed cell clones within the gastrointestinal mucosa.