Deciphering Diseases and Biological Targets for Environmental Chemicals using Toxicogenomics Networks

Exposure to environmental chemicals and drugs may have a negative effect on human health. A better understanding of the molecular mechanism of such compounds is needed to determine the risk. We present a high confidence human protein-protein association network built upon the integration of chemical toxicology and systems biology. This computational systems chemical biology model reveals uncharacterized connections between compounds and diseases, thus predicting which compounds may be risk factors for human health. Additionally, the network can be used to identify unexpected potential associations between chemicals and proteins. Examples are shown for chemicals associated with breast cancer, lung cancer and necrosis, and potential protein targets for di-ethylhexyl-phthalate, 2,3,7,8-tetrachlorodibenzo-p-dioxin, pirinixic acid and permethrine. The chemical-protein associations are supported through recent published studies, which illustrate the power of our approach that integrates toxicogenomics data with other data types

Impact of growing conditions and foliar nutrition on growth and development of Spanish bluebell (Hyacinthoides hispanica (Mill.) Rothm.)

Hyacinthoides hispanica (Mill.) Rothm. is a valuable bulbous ornamental plant grown in parks and gardens. It comes from the Iberian Peninsula, hence its cultivation under Polish conditions may be inefficient. The purpose of the study was to determine the effect of growing conditions and foliar feeding using phosphorous fertilizer on the growth and decorative qualities of H. hispanica. It was found that the pine bark layer effectively protected the plants from freezing, which had a beneficial effect on their growth and flowering characteristics. Flowering of plants grown without the mulch was minimal, which clearly indicates that mulching of the soil under H. hispanica can be necessary. Plants grown using the mulch produced more and longer leaves, and also formed more inflorescences and fruits as well as longer inflorescence stems. The addition of peat to the soil did not favour the growth and decorative qualities of H. hispanica, while foliar nutrition with phosphorous had a positive effect. In addition, the decorative values of H. hispanica were influenced by the interaction of soil mulching with bark and foliar feeding. Plants grown in this combination had more inflorescences, which were higher, composed of more flowers in the inflorescence and reached a greater diameter than non-fertilized ones. Tested cultivars of H. hispanica differed in their features of growth and flowering

A novel biomarker for anti-androgenic activity in placenta reveals risks of urogenital malformations

It has been hypothesized that the rise in male reproductive disorders over recent decades may at least be partially attributable to environmental factors, including chemical exposures, but observed associations with single chemicals were rather weak. The aim of this case-control study was to explore the relationship between exposure to mixtures of (anti-) androgenic chemicals during pregnancy and the risk of cryptorchidism and/or hypospadias in offspring, using the total effective xenobiotic burden of anti-androgens (TEXB-AA) as a biomarker. A subsample of 29 cases (16 of cryptorchidism, 12 of hypospadias, and one of both disorders) and 60 healthy controls was nested in a cohort of male newborns recruited between October 2000 and July 2002. The (anti-) androgenic activity of placenta samples collected at delivery was assessed using TEXB-AA biomarker, combined with a bioassay-directed fractionation protocol that separated endogenous hormones from most (anti-) androgenic chemicals by normal-phase HPLC. The bioassay measures the androgen-induced luciferase activity and the inhibition of this pathway by (anti-) androgens. First, we collected 27 HPLC fractions in each placenta extract, which were all tested in the bioassay. The multivariable statistical analyses indicated a statistically significant positive dose-response association between the potent anti-androgenic activity of the HPLC fraction collected during minutes 1-2 (F2) and the risk of malformations (odds ratio: 2.33, 95% CI: 1.04-5.23). This study represents a novel approach for the estimation of combined effects of the total anti-androgenic load and the associations suggest an effect of environmental pollutants on the development of fetal reproductive tract