Reference

Effect of dietary indole-3-carbinol on intestinal and hepatic monooxygenase, glutathione S-transferase and epoxide hydrolase activities in the rat

Effect of dietary indole-3-carbinol on intestinal and hepatic monooxygenase, glutathione S-transferase and epoxide hydrolase activities in the rat. Bradfield, C. A.; Bjeldanes, L. F. (Dep. Nutr. Sci., Univ. California, Berkeley, CA 94720, USA). Food Chem. Toxicol., 22(12), 977-82 (English) 1984. CODEN: FCTOD7. ISSN: 0278-6915. DOCUMENT TYPE: Journal CA Section: 17 (Food and Feed Chemistry) Section cross-reference(s): 4 Male Sprague-Dawley rats were fed purified diets supplemented with 50-500 ppm indole-3-carbinol (I3C) [700-06-1], a compd. present in cruciferous vegetables, or with 25% Brussels sprouts (Brassica oleracea), for 10 days after a 1-wk equilibration on a purified diet. Cytosolic and microsomal fractions were prepd. from liver and intestinal mucosae. Intestinal aryl hydrocarbon hydroxylase (AHH) [9037-52-9] activity was increased over basal levels by I3C at 50 ppm (a 6.1-fold increase), at 125 ppm (11.8-fold), at 250 ppm (14.1-fold) and at 500 ppm (20.2-fold) and by 25% Brussels sprouts (3.6-fold). Intestinal ethoxycoumarin O-deethylase (ECD) [42613-26-3] activity was also increased by I3C, the increases being 4.6-, 8.7-, 9.3- and 11.2-fold with 50, 125, 250 and 500 ppm I3C, resp., and 3.2-fold with the sprouts diet. Hepatic AHH and ECD were not increased by any of these dietary treatments. Hepatic and intestinal glutathione S-transferase (GST) [50812-37-8] activities were increased 1.9- and 1.6-fold, resp., by the sprouts diet but were not affected even by 500 ppm I3C. Microsomal epoxide hydrolase (EH) [9048-63-9] activity of the small intestine was increased 2.0-fold by the sprouts diet but was unaffected by I3C. Hepatic cytochrome P 450 [9035-51-2] was increased 1.3-fold by the sprouts diet, although I3C at 500 ppm only produced a 1.1-fold increase. A no-effect-level for I3C on intestinal monooxygenase [9038-14-6] induction was 16-25 ppm, supporting the contention that I3C can account for much of the monooxygenase induction obsd. when exptl. animals are fed diets high in cruciferous vegetables. B. oleracea Contains other compds. which are responsible for the induction of GST and EH activities.

Effects of dietary indoles and isothiocyanates on N-nitrosodimethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone a-hydroxylation and DNA methylation in rat liver

Effects of dietary indoles and isothiocyanates on N-nitrosodimethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone a-hydroxylation and DNA methylation in rat liver. Chung, Fung Lung; Wang, Minyao; Hecht, Stephen S. (Naylor Dana Inst. Dis. Prev., Am. Health Found., Valhalla, NY 10595, USA). Carcinogenesis (London), 6(4), 539-43 (English) 1985. CODEN: CRNGDP. ISSN: 0143-3334. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Dietary-related indoles, isothiocyanates, and the allyl isothiocyanate glucosinolate, sinigrin [3952-98-5], were administered to F344 rats in the diet for 2 wk (chronic protocol) or by gavage 2 h before sacrifice (acute protocol) and the effects of these pretreatments on the a-hydroxylation of 2 carcinogenic nitrosamines, N-nitrosodimethylamine (NDMA) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NKK), were evaluated. a-Hydroxylation was measured in vitro by quantitation of HCHO formation upon incubation of the nitrosamines with liver microsomes, and in vivo by quantitation of levels of 7-methylguanine and O6-methylguanine in hepatic DNA, 4 h after nitrosamine treatment. Compds. shown to be inhibitory in the in vitro assay were selected to be further evaluated using the in vivo assay. The results of the in vitro assays showed that indoles were inducers of the demethylation of both nitrosamines. Indole [120-72-9], L-tryptophan [73-22-3], and indole-3-carbinol [700-06-1] were strong inducers of NDMA and NNK demethylation, resp. In contrast, isothiocyanates, such as phenethyl isothiocyanate [2257-09-2] and phenyl isothiocyanate [103-72-0] demonstrated a wide range of inhibitory activities toward demethylation of these nitrosamines in acute and chronic studies. Chronic, but not acute, pretreatment with sinigrin also caused a significant decrease in the demethylation of NDMA and NNK. In view of their promising inhibitory activities, the effects of phenethyl isothiocyanate, Ph isothiocyanate, and sinigrin on the in vivo methylation of DNA by NDMA and NNK were evaluated. The results were parallel to those obtained in the in vitro assays. Phenethyl isothiocyanate, Ph isothiocyanate, and sinigrin generally inhibited the formation of 7-methylguanine and O6-methylguanine in rat hepatic DNA. The results of this study suggest that these compds. could be anticarcinogenic to NDMA and NNK.