Gilbert S. Stoewsand

Bioactive organosulfur phytochemicals in Brassica oleracea vegetables—A review

Sulfur-containing phytochemicals of two different kinds are present in all Brassica oleracea (Cruciferae) vegetables (cabbage, broccoli, etc.). They are glucosinolates (previously called thioglucosides) and S-methyl cysteine sulfoxide. These compounds, which are derived in plant tissue by amino acid biosynthesis, show quite different toxicological effects and appear to possess anticarcinogenic properties. Glucosinolates have been extensively studied since the mid-nineteenth century. They are present in plant foods besides Brassica vegetables with especially high levels in a number of seed meals fed to livestock. About 100 different kinds of glucosinolates are known to exist in the plant kingdom, but only about 10 are present in Brassica. The first toxic effects of isothiocyanates and other hydrolytic products from glucosinolates that were identified were goitre and a general inhibition of iodine uptake by the thyroid. Numerous studies have indicated that the hydrolytic products of at least three glucosinolates, 4-methyl-sulfinylbutyl (glucoraphanin), 2-phenylethyl (gluconasturtiin) and 3-indolylmethyl (glucobrassicin), have anticarcinogenic activity. Indole-3-carbinol, a metabolite of glucobrassicin, has shown inhibitory effects in studies of human breast and ovarian cancers. Kale poisoning, or a severe haemolytic anaemia, was discovered in cattle in Europe in the 1930s, but its link with the hydrolytic product of S-methyl cysteine sulfoxide was only shown about 35 years later. S-methyl cysteine sulfoxide and its metabolite methyl methane thiosulfinate were shown to inhibit chemically-induced genotoxicity in mice. Thus, the cancer chemopreventive effects of Brassica vegetables that have been shown in human and animal studies may be due to the presence of both types of sulfur-containing phytochemicals (i.e. certain glucosinolates and S-methyl cysteine sulfoxide).

Modification by beet and cabbage diets of aflatoxin B1-induced rat plasma α-foetoprotein elevation, hepatic tumorigenesis, and mutagenicity of urine

Weanling male Fischer rats were fed a purified diet or diets containing 25% (w/w) freeze-dried ground beets or cabbage with or without 1 ppm aflatoxin B1 (AFB1) for 26 wk. In 3-7 wk the cabbage diet diminished, while the beet diet enhanced AFB1-induced plasma alpha-foetoprotein (AFP) elevation. When the experiment was extended to 42 wk by maintaining the animals on the purified (basal) diet for a further 16 wk the rats that had consumed AFB1 in the beet diet had 72 +/- 14 tumours/liver (mean surface diameter of tumours, 6.13 +/0 4.69 mm); animals that had been given AFB1 in the control diet had 30 +/- 16 tumours/liver (mean surface diameter, 4.36 +/- 3.16 mm); rats that had been given AFB1 in the cabbage diet had 13 +/- 5 tumours/liver (mean surface diameter, 4.28 +/- 2.89 mm). In the Salmonella/mammalian microsomal test, urine from rats fed AFB1 with beets caused significantly (P less than 0.05) more revertants in Salmonella typhimurium strain TA98 than did urine from rats fed AFB1 with purified or cabbage diets. The beet- and cabbage-containing diets had no effect on the plasma AFP concentration, hepatic tumorigenesis, or the mutagenicity of urine in rats receiving no AFB1. The evidence suggests that non-nutrient components of common vegetables may influence the response to chemical carcinogens, and that AFP determinations are useful in the rapid identification of dietary factors that modify carcinogenesis.

Dietary selenium protection of methylmercury intoxication of Japanese quail

SummarySelenium, as sodium selenite, added at 5 ppm to purified diets of Japanese quail protected against methylmercury intoxication. Selenium fed simultaneously with methylmercury to quail for 9 weeks gave complete protection. However, feeding selenium with methylmercury for 4 weeks, followed by a diet containing only methylmercury, delayed the onset of methylmercury intoxication for 1–2 weeks as compared to quail not pretreated with selenium. On diets which contained 20 ppm of methylmercury but no selenium, over 90% mortality was observed for young quail within 2 weeks, and mature quail within 4 weeks. Methylmercury residues in liver, kidney, and brain are higher in male than female quail. High methylmercury content of these organs, or in produced eggs, does not indicate that birds will show evidence of methylmercury toxicosis.

Protective effect of dietary brussels sprouts against mammary carcinogenesis in Sprague-Dawley rats

The effect of dietary brussels sprouts (Brassica oleracea, L.) on mammary carcinogenesis induced by 7,12-dimethylbenz[a]anthracene (DMBA) was studied in Sprague-Dawley female rats. Rats fed a 20% brussels sprouts diet only during the initiation period of carcinogenesis had a palpable mammary tumor incidence of 13%, while those fed a casein-cornstarch semi-purified diet during this initiation period had a tumor incidence of 77% after 15 weeks post DMBA dose. When the rats were switched from the semi-purified diet to the 20% brussels sprouts diet at this time, there appeared to be a regression of small mammary tumors after 6 weeks on this dietary treatment. This regression was transitory since during the final 10 weeks of this 1 year study, 100% of this group of rats developed tumors. The rats fed the 20% brussels sprouts diet during tumor initiation exhibited a 67% incidence of fibroadenomas. The rats fed the semi-purified diet during initiation, but switched later to the brussels sprouts diet, showed over a 90% incidence of adenocarcinomas.

Quercetin: A mutagen, not a carcinogen, in fischer rats

Purified quercetin, as well as diets containing quercetin at 0.1% and 0.2%, are mutagens to Salmonella typhimurium TA100. This mutagenicity is enhanced with the S9 metabolic activation system. The urine of Fischer rats fed the 0.2% quercetin diet also is mutagenic with the S9 activation system, but the feces of these animals exhibited enhanced mutagenicity only without activation. This may indicate different quercetin metabolites in urine and feces. Rats fed these diets for 64 wk showed no consistent tissue lesions, carcinogenicity, or reproductive changes. Male rats fed 0.2% quercetin showed lowered blood serum glutamic oxaloacetic transaminase and urea nitrogen levels, but these values do not reflect pathological changes.

Eggshell thinning in Japanese quail fed mercuric chloride

The eggs produced by developing Japanese quail (Coturnix coturnix japonica) fed 1 to 8 parts of mercury per million as mercuric chloride for 10 weeks have thinned shells. Total amounts of mercury in tissues were quite proportional to the dosage and were higher in males than in females. Methylation of mercury was not observed.

Inhibition of benzo[a]pyrene-induced bone marrow micronuclei formation by diallyl thioethers in mice.

Diallyl thioethers (DATEs), naturally occurring compounds present in garlic, were investigated for their putative ability to inhibit benzo[a]pyrene-induced genotoxicity in ICR and C3H strains of mice. The mouse bone marrow micronucleus assay was used as an indicator of in vivo genotoxicity. A dose of 0.67 mmol total DATEs/kg body weight inhibited formation of micronucleated polychromatic erythrocytes (MPCEs) by 24%, and 0.33 mmol DATEs inhibited formation of MPCEs by 45%. Possibly the toxicity of DATEs accounted for less inhibition with the higher dose. Formation of MPCEs were inhibited only slightly by DATEs in C3H mice. These results indicate that the mouse bone marrow micronucleus assay can be used to identify organosulfur components of garlic that inhibit genotoxicity.

Hepatic glutathione S-transferase activity and aflatoxin B1-induced enzyme altered foci in rats fed fractions of brussels sprouts

The aim of the present study was to determine whether the liver cytosol detoxication enzymes, glutathione S-transferases (GSTases) as well as gamma-glutamyl transpeptidase (GGT) foci induced by aflatoxin B1 (AFB) were changed by feeding weanling rats diets containing brussels sprouts, a glucosinolate fraction of brussels sprouts (extract), or a non-glucosinolate fraction (residue). All 3 of these diets induced high levels of hepatic GSTase specific activity as compared to purified-basal diet fed control rats. The brussels sprouts and the extract treatments, but not the residue dietary treatment, inhibited hepatic GGT foci induced by AFB. Thus, glucosinolates and non-glucosinolate fractions of brussels sprouts induce hepatic enzymes involved in detoxication mechanisms but the non-glucosinolate compound(s) apparently are not involved in all chemical carcinogen metabolic processes.

Study of guinea pigs fed Swiss chard grown on municipal sludge-amended soil. Multi-element content of tissues.

Swiss chard, field-grown on soil amended with 100 dry tons per acre of municipal sewage sludge from Washington, DC, was fed to guinea pigs for 28 days. Control animals were fed Swiss chard grown on unfortified soi. Forty-one elements were determined in the sludge, the plant material, and liver, kidney, muscle, adrenal, and spleen tissues by neutron activation and other methods. Elevated concentrations of several elements found in the Swiss chard grown on the sludge-soil mixture also appeared at higher levels in certain of the animal tissues. These included antimony in adrenal, cadmium in kidney, manganese in liver tissues, and tin in several tissues. The animals showed no observable toxicological effects.

Effect of dietary brussels sprouts with increased selenium content on mammary carcinogenesis in the rat

Brussels sprouts (Brassica oleracea, L; Jade cross E, hybrid cultivar) were cultivated with inorganic selenium added to the plant growth medium. Sprague-Dawley, female, weanling rats were divided into groups and fed 20% brussels sprouts diets containing either 0.03, 0.58, 1.29, or 6.71 ppm of selenium naturally occurring in the sprouts. These diets were fed 2 weeks before and 2 weeks after a single dose of 7,12-dimethylbenz[a]anthracene (DMBA), and the rats were then placed on a low selenium basal diet for an additional 25 weeks. All brussels sprouts diets reduced the incidence of DMBA-induced mammary carcinogenesis. Increased dietary levels of naturally occurring selenium did not further depress mammary tumorigenesis. The time periods of selenium feeding may have been too brief to observe any additional tumor reductions.