The effects of dietary
sinigrin and
indole-3-carbinol (I3C) on DNA methylation and O6-methylguanine--DNA-transmethylase activity, factors which may be of importance in the induction of tumorigenicity by the tobacco-specific
nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), were investigated. Additionally, the effects of dietary
sinigrin on NNK tumorigenicity were assessed in a two-year bioassay in F344 rats. DNA methylation in target tissues of NNK
tumorigenesis was examined in F344 rats administered [3H-CH3]NNK (0.6 mg/kg, four doses) s.c. and fed control or experimental diets for two weeks. Dietary
sinigrin at a concentration of 3 mumol/g diet decreased
7-methylguanine formation in hepatic
DNA, but had no effect on
7-methylguanine levels of lung or nasal mucosa
DNA. Dietary I3C at a concentration of 30 mumol/g diet increased
7-methylguanine levels in hepatic
DNA, but decreased DNA methylation in lung and nasal mucosa. No effects on O6-methylguanine--DNA-transmethylase activity were observed in
tissue extracts derived from the livers, lungs and nasal mucosae of rats fed diets containing
sinigrin or I3C. These results suggested that dietary
sinigrin might reduce the incidence of NNK-induced hepatic
tumors with no effect on NNK
tumorigenesis of the lung and nasal cavity, whereas I3C might increase hepatic
tumor incidence and reduce NNK
tumorigenesis of the lung and nasal cavity. The bioassay results showed that dietary
sinigrin had no effect on NNK
tumorigenesis in these target tissues. However, dietary
sinigrin plus NNK resulted in a significant incidence of pancreatic
tumors, a rare occurrence in F344 rats. While the results from DNA methylation studies are in agreement with the bioassay data for lung and nasal cavity, the absence of any inhibitory effect of dietary
sinigrin on NNK hepatic
tumorigenesis indicates that factors other than DNA methylation and
O6-methylguanine repair should be considered in assessing the effects of dietary compounds on NNK hepatic
tumorigenesis. The contrary effects on NNK-induced hepatic DNA methylation by
sinigrin and I3C, two major components of cruciferous vegetables, demonstrate the complexities of dietary modulation of
carcinogenesis.