Carcinogenesis, Vol 19, 267-273, Copyright © 1998 by Oxford University Press
TK Smith, EK Lund and IT Johnson
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.
ARTICLES
Inhibition of dimethylhydrazine-induced aberrant crypt foci and induction of apoptosis in rat colon following oral administration of the glucosinolate sinigrin
Institute of Food Research, Norwich Laboratory, Colney, UK.
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