Formation of hepatic DNA adducts by methyleugenol in mouse models: drastic decrease by Sult1a1 knockout and strong increase by transgenic human SULT1A1/2.

Methyleugenol--a natural constituent of herbs and spices--is hepatocarcinogenic in rodent models. It can form DNA adducts after side-chain hydroxylation and sulfation. We previously demonstrated that human sulfotransferases (SULTs) 1A1 and 1A2 as well as mouse Sult1a1, expressed in Salmonella target strains, are able to activate 1'-hydroxymethyleugenol (1'-OH-ME) and 3'-hydroxymethylisoeugenol (3'-OH-MIE) to mutagens. Now we investigated the role of these enzymes in the formation of hepatic DNA adducts by methyleugenol in the mouse in vivo. We used FVB/N mice [wild-type (wt)] and genetically modified strains in this background: Sult1a1 knockout (ko), transgenic for human SULT1A1/2 (tg) and the combination of both modifications (ko-tg). Methyleugenol (50mg/kg body mass) formed 23, 735, 3770 and 4500 N (2)-(trans-methylisoeugenol-3'-yl)-2'-deoxyguanosine adducts per 10(8) 2'-deoxyribonucleosides (dN) in ko, wt, ko-tg and tg mice, respectively. The corresponding values for an equimolar dose of 1'-OH-ME were 12, 1490, 12 400 and 13 300 per 10(8) dN. Similar relative levels were observed for the minor adduct, N (6)-(trans-methylisoeugenol-3'-yl)-2'-deoxyadenosine. Thus, the adduct formation by both compounds was nearly completely dependent on the presence of SULT1A enzymes, with human SULT1A1/2 producing stronger effects than mouse Sult1a1. Moreover, a dose of 0.05 mg/kg methyleugenol (one-fourth of the estimated average daily exposure of humans) was sufficient to form detectable adducts in humanized (ko-tg) mice. Although 3'-OH-MIE was equally mutagenic to 1'-OH-ME in Salmonella strains expressing human SULT1A1 or 1A2, it only formed 0.14% of hepatic adducts in ko-tg mice compared with an equimolar dose of 1'-OH-ME, suggesting an important role of detoxifying pathways for this isomer in vivo.

Health benefits and possible risks of broccoli - an overview.

Chemopreventive effects of broccoli, a highly valued vegetable, have been known for a long time. Several studies have demonstrated that broccoli might be beneficial by reducing the risk for the development of certain forms of cancer. These effects are generally attributed to glucosinolate-derived degradation products like isothiocyanates and indoles which are formed by the hydrolytic action of plant myrosinase and/or glucosidases deriving from the human microbial flora. However, recent in vitro and experimental animal studies indicate that broccoli, its extracts and the glucosinolate-derived degradation products might also have undesirable effects, especially genotoxic activities. However, the relevance of the genotoxic activities to human health is not known yet. This paper gives an overview on genotoxic, anti-genotoxic/chemopreventive, nutritive and antinutritive properties of broccoli, its ingredients and their degradation products. A qualitative comparison of the benefit and risk of broccoli consumption benefit-risk assessment shows that the benefit from intake in modest quantities and in processed form outweighs potential risks. For other preparations (fortified broccoli-based dietary supplements, diets with extraordinary high daily intake, consumption as a raw vegetable) further studies both for potential risks and beneficial effects are needed in order to assess the benefit and risk in the future.

Risks and benefits of dietary isoflavones for cancer.

A high intake of fruits and vegetables is associated with a lower risk of cancer. In this context, considerable attention is paid to Asian populations who consume high amounts of soy and soy-derived isoflavones, and have a lower risk for several cancer types such as breast and prostate cancers than populations in Western countries. Hence, interest focuses on soyfoods, soy products, and soy ingredients such as isoflavones with regard to their possible beneficial effects that were observed in numerous experiments and studies. The outcomes of the studies are not always conclusive, are often contradictory depending on the experimental conditions, and are, therefore, difficult to interpret. Isoflavone research revealed not only beneficial but also adverse effects, for instance, on the reproductive system. This is also the case with tumor-promoting effects on, for example, breast tissue. Isoflavone extracts and supplements are often used for the treatment of menopausal symptoms and for the prevention of age-associated conditions such as cardiovascular diseases and osteoporosis in postmenopausal women. In relation to this, questions about the effectiveness and safety of isoflavones have to be clarified. Moreover, there are concerns about the maternal consumption of isoflavones due to the development of leukemia in infants. In contrast, men may benefit from the intake of isoflavones with regard to reducing the risk of prostate cancer. Therefore, this review examines the risks but also the benefits of isoflavones with regard to various kinds of cancer, which can be derived from animal and human studies as well as from in vitro experiments.

Toxicological assessment of 3-chloropropane-1,2-diol and glycidol fatty acid esters in food.

Fatty acid esters of 3-chloropropane-1,2-diol (3-MCPD) and glycidol are a newly identified class of food process contaminants. They are widespread in refined vegetable oils and fats and have been detected in vegetable fat-containing products, including infant formulas. There are no toxicological data available yet on the 3-MCPD and glycidol esters, and the primary toxicological concern is based on the potential release of 3-MCPD or glycidol from the parent esters by lipase-catalyzed hydrolysis in the gastrointestinal tract. Although 3-MCPD is assessed as a nongenotoxic carcinogen with a tolerable daily intake (TDI) of 2 µg/kg body weight (bw), glycidol is a known genotoxic carcinogen, which induces tumors in numerous organs of rodents. The initial exposure estimates, conducted by Federal Institute for Risk Assessment (BfR) under the assumption that 100% of the 3-MPCD and glycidol are released from their esters, revealed especially that infants being fed commercial infant formula could ingest harmful amounts of 3-MCPD and glycidol. However, the real oral bioavailability may be lower. As this gives rise for toxicological concern, the currently available toxicological data of 3-MCPD and glycidol and their esters are summarized in this review and discussed with regard to data gaps and further research needs.