Increased induction of aberrant crypt foci by 1,2-dimethylhydrazine in rats fed diets containing purified genistein or genistein-rich soya protein.
The isoflavonoid genistein inhibits mitosis and increases apoptosis in a variety of tumour cell lines in vitro, and may exert anticarcinogenic effects in vivo. To assess its effects on the colon, rats were fed a semi-synthetic control diet, or similar diets enriched with genistein (0.25 g/kg), either as the pure isoflavone or as part of a soya protein isolate, for 7 days before receiving subcutaneous injections of saline or 1,2-dimethylhydrazine (DMH). After 48 h, rats given saline were killed and samples of their small and large intestinal mucosa were obtained for assessment of crypt cell mitosis and apoptosis by visual analysis of isolated intact crypts. Rats given DMH were fed control diet and killed after 48 h for assessment of crypt cytokinetics or maintained for 42 days then killed and their colonic mucosa analysed for aberrant crypt foci (ACF). Two further groups were given control diet before DMH, followed by the genistein or soya-based diet for 42 days before assessment of ACF. Neither genistein nor soya protein isolate had a significant effect on crypt cell mitosis or apoptosis in untreated rats, or on the proliferative response to treatment with DMH. However, consumption of pure genistein or the soya protein isolate before treatment with DMH was associated with a 3-fold (P < 0.001) or 2-fold (P < 0.05) increase, respectively, in ACF in the distal colon. There was no significant effect of genistein or soya protein isolate given after DMH treatment. We conclude that genistein has no detectable effect on colonic crypt mitosis or apoptosis in the rat in vivo, but that it promotes induction of ACF by an as yet undefined mechanism when fed immediately before treatment with DMH.
Gee
J M
JM
Institute of Food Research, Norwich Research Park, Colney, Norwich, Norfolk NR4 7UA, UK.
Noteborn
H P
HP
Polley
A C
AC
Johnson
I T
IT
D019813:1,2-Dimethylhydrazine / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D003106:Colon / Q000187:drug effects* / Q000473:pathology; D019833:Genistein / Q000008:administration & dosage / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D007421:Intestine, Small / Q000166:cytology / Q000187:drug effects; D008297:Male; D008938:Mitosis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D030262:Soybean Proteins; D015430:Weight Gain / Q000187:drug effects
D016588:Anticarcinogenic Agents; D030262:Soybean Proteins; D019833:Genistein; D019813:1,2-Dimethylhydrazine