The potential for dispersant use as a maritime oil spill response measure in German waters.

In case of an oil spill, dispersant application represents a response option, which enhances the natural dispersion of oil and thus reduces coating of seabirds and coastal areas. However, as oil is transferred to the water phase, a trade-off of potential harmful effects shifted to other compartments must be performed. This paper summarizes the results of a workshop on the current knowledge on risks and benefits of the use of dispersants with respect to specific conditions encountered at the German sea areas. The German North Sea coast is a sensitive ecosystem characterised by tidal flats, barrier islands and salt marshes. Many prerequisites for a potential integration of dispersants as spill response option are available in Germany, including sensitivity maps and tools for drift modelling of dispersed and undispersed oil. However, open scientific questions remain concerning the persistence of dispersed oil trapped in the sediments and potential health effects.

Dry bulk cargo shipping - An overlooked threat to the marine environment?

Approximately 9.5billiontonnes of goods is transported over the world oceans annually with dry bulk representing the largest cargo group. This paper aims to analyse whether the transport and associated inputs of dry bulks into the sea create a risk for the marine environment. For this purpose, we analyse the international regulatory background concerning environmental protection (MARPOL), estimate quantities and identify inputs of such cargoes into the oceans (accidental and operational), and use available information for hazard assessment. Annually, more than 2.15milliontonnes of dry bulk cargoes are likely to enter the oceans, of which 100,000tonnes are potentially harmful to the marine environment according to the definition included in draft maritime regulation. The assessment of the threat to the marine environment is hampered by a lack of available information on chemical composition, bioavailability and toxicity. Perspectives for amendments of the unsatisfying pollution prevention regulations are discussed.

Genetic association between obstructive bronchitis and enzymes of oxidative stress.

OBJECTIVE: Obstructive respiratory diseases, mainly the chronic obstructive pulmonary disease (COPD) and asthma, are associated with functional polymorphisms of xenobiotic-metabolizing enzymes (XMEs). To date, association for obstructive bronchitis has not been described. MATERIAL/METHODS: In this study, we investigated the genotypes from 26 functional polymorphisms of 20 XMEs in children (n, 1028) at the age of 6 years from the German prospective birth cohort study (LISAplus) and analyzed the associations between genotypes and obstructive bronchitis. RESULTS: For the first time, we found noteworthy gene-disease associations for the functional PON1 M55L and EPHX1 H139R polymorphisms and gene-environment associations for the functional COMT V158M and NQO1 P187S polymorphisms after stratification for maternal active smoking behaviour during pregnancy. The noteworthy associations were substantiated by the biological findings that all the risk genotypes belong to genes involved in oxidative stress and code for proteins with a fast enzymatic activity or concomitantly appear in common estrogene-metabolizing pathway (COMT, NQO1). CONCLUSION: The oxidative stress has to be taken into account in mechanism of the obstructive bronchitis in early childhood. The risk genotypes may serve as risk factors for respiratory obstruction rather than for signs of COPD or asthma.

Cement-related particles interact with proinflammatory IL-8 chemokine from human primary oropharyngeal mucosa cells and human epithelial lung cancer cell line A549.

Epidemiological studies have shown that respirable exposure to emitted cement particulate matter is associated with adverse health risk for human. The underlying mechanisms, however, are poorly understood. To examine the effect of cement, nine blinded cement-related particulates (<10 µm) were assessed with regard to their induction of the proinflammatory cytokines IL-6 and IL-8 in human primary epithelial cells (pEC) from oropharyngeal mucosa as well as from nonsmall-cell lung carcinoma (non-SCLC) cells A549. It was demonstrated that the cement specimens did not act cytotoxic as assessed by the lactate dehydrogenase (LDH) assay. The basal and IL-1ß-induced IL-8 expression was suppressed, in contrast to an unchanged IL-6. At the transcript level the basal and induced IL-6 and IL-8 gene expression was not influenced by cement dust. To discover the mechanism by which cement influenced the IL-8 expression the following experiments were performed. Submerse exposure experiments have shown that the release of IL-8 was suppressed by cement dust. Furthermore, the incubation of IL-8 with cement-related specimens under cell-free condition led to a loss of immunoreactive IL-8. An immunological masking of IL-8 by free soluble components of respiratory epithelial cells was excluded. Thus, the decrease of IL-8 protein content after cement exposure seems to be a result of the adsorption of IL-8 protein to cement particles and the inhibition of IL-8 release. In conclusion, due to absent cytotoxic and inflammatory effects of cement-related specimens in both human pEC and A549 cell models it remains open how cement exposure may lead to the respiratory adverse effects in humans.

Transcriptional signatures of regulatory and toxic responses to benzo-[a]-pyrene exposure.

BACKGROUND: Small molecule ligands often have multiple effects on the transcriptional program of a cell: they trigger a receptor specific response and additional, indirect responses ("side effects"). Distinguishing those responses is important for understanding side effects of drugs and for elucidating molecular mechanisms of toxic chemicals. RESULTS: We explored this problem by exposing cells to the environmental contaminant benzo-[a]-pyrene (B[a]P). B[a]P exposure activates the aryl hydrocarbon receptor (Ahr) and causes toxic stress resulting in transcriptional changes that are not regulated through Ahr. We sought to distinguish these two types of responses based on a time course of expression changes measured after B[a]P exposure. Using Random Forest machine learning we classified 81 primary Ahr responders and 1,308 genes regulated as side effects. Subsequent weighted clustering gave further insight into the connection between expression pattern, mode of regulation, and biological function. Finally, the accuracy of the predictions was supported through extensive experimental validation. CONCLUSION: Using a combination of machine learning followed by extensive experimental validation, we have further expanded the known catalog of genes regulated by the environmentally sensitive transcription factor Ahr. More broadly, this study presents a strategy for distinguishing receptor-dependent responses and side effects based on expression time courses.

Maternal fine particulate matter exposure, polymorphism in xenobiotic-metabolizing genes and offspring birth weight.

We aimed to describe if polymorphisms in xenobiotics-metabolizing genes modify the effect of maternal exposure to fine particulate matter (PM(2.5)) on offspring birth weight. Among newborns from LISA cohort, we tested if polymorphisms of GSTT1, GSTP1, GSTM1, and CYP2D6 genes modified the effect measure of PM(2.5) on term birth weight. Subsequently, we tested if polymorphisms modified the effect of other exposure factors with possibly similar pathways of action (active or passive smoking). PM (2.5) exposure above the median value (reference, below) was associated with birth weight changes by 76 g in the homozygous wild type genotype (n=161), -90 g in the heterozygous genotype (n=154) and -168 g in children with GSTP1 *1B/*1B mutant genotype (n=39, interaction test, p=0.05). No effect measure modification with PM(2.5) was detected for GSTT1, GSTM1 or CYP2D6 polymorphisms (p≥ 0.12). No effect measure modification with GSTP1 polymorphism was detected for active (p=0.71) nor for passive smoking effects on birth weight (p=0.13).

Diversity of common alternative splicing variants of human cytochrome P450 1A1 and their association to carcinogenesis.

Cytochrome P450 1A1 (CYP1A1) belongs to the enzymes of biotransformation of phase I. CYP1A1 performs the catalytic activation of exogenous and endogenous substrates to more carcinogenic metabolites. Overexpression of the wild-type and a recently described splice variant (CYP1A1v, ovarian cancer) are attributed to neoplastic transformation. Here we describe novel CYP1A1 splicing variants commonly and frequently transcribed in leucocytes of healthy volunteers, separated from variants exclusively expressed in tumour cell lines. Interestingly, all the novel splicing variants in leukocytes are generated by employing of two nested splice site pairs, one outer canonical and one inner non-canonical splice site pair, within the exon 2 of the human CYP1A1. In general, the frequent presence of common splicing variants in healthy volunteers has to be consider as a physiological feature of human CYP1A1 transcription process, rather than a signature of carcinogenesis.

Cytotoxicity and oxidative stress caused by chemicals adsorbed on particulate matter.

Air particulate matter (PM) and bound chemicals are potential mediators for adverse health effects. The cytotoxicity and changes in energy-providing processes caused by chemical compounds bound to PM of different size fractions were investigated in Tetrahymena pyriformis. The PM samplings were carried out using a high volume cascade impactor (6 size fractions between 10 microm and less than 0.49 microm) at three points of La Plata, Argentina: in an industrial area, a traffic-influenced urban area, and a control area. Extracts from respirable particles below 1 mum initiated the highest cytotoxic effects, demonstrating their higher risk. In contrast, an increase on oxygen consumption was observed especially in tests of extracts from particles less than 1 mum from urban and industrial areas. The increase on oxygen consumption could be caused by decoupling processes in the respiratory chain. Otherwise the ATP concentration was increased too, even though to a lower extent. The observed imbalance between oxygen consumption and ATP concentration in exposed T. pyriformis cells may be due to oxidative stress, caused by chemical compounds bound to the particles. Owing to the complexity of effects related to PM and their associated chemical compounds, various physiological parameters necessarily need to be investigated to obtain more information about their possible involvement in human relevant pathogenic processes. As shown here, effects on cell proliferation and on energy-providing processes are suitable indicators for the different impact of PM and adsorbed chemicals from various sampling locations.