Glucosinolates are sulphur compounds that occur as
glycosides in brassica vegetables. In response to tissue disruption they are degraded by
thioglucosidase, releasing a range of highly reactive breakdown products, including the
isothiocyanates, which we have previously shown to be selectively cytotoxic to undifferentiated colorectal tumour cells (HT29). In the present study we explored the effect of
sinigrin on the intestinal mucosa of rats previously treated with
dimethylhydrazine (
DMH). In the first experiment, a semisynthetic feed containing
sinigrin (400 microg/g diet) was provided 6 h after the second of two
injections of
DMH. The level of apoptosis was measured by morphological assessment of intact microdissected crypts obtained at 18, 24, 38, 48 and 72 h after injection, and compared with control groups given
DMH only, or a
sham-injection. Higher numbers of apoptotic nuclei were present in colonic tissue from both groups of
DMH-treated rats compared with the controls, and the level was significantly higher in
DMH-treated rats fed
sinigrin compared with those given
DMH only (P < 0.02). In a second experiment, rats were given
sinigrin (400 microg/g diet) 22 h after the second of two
injections of
DMH; the level of apoptosis was measured after 48 h and the numbers of
aberrant crypt foci (ACF) were measured after 42 days. The level of apoptosis was significantly higher in
DMH-treated rats given
sinigrin compared with controls (P < 0.05), and the numbers of ACF were significantly lower in
sinigrin-treated rats (P < 0.001). There was no statistically significant induction of apoptosis in animals fed
sinigrin alone.
Sinigrin administered after
DMH suppresses induction of ACF. This may be due to increased apoptotic deletion of damaged stem cells in the crypts of animals fed
sinigrin.