There is a growing awareness about the need to comprehensively integrate sex and gender into health research in order to enhance the validity and significance of research results. An in-depth consideration of differential exposures and vulnerability is lacking, especially within environmental risk assessment. Thus, the interdisciplinary team of the collaborative research project INGER (integrating gender into environmental health research) aimed to develop a multidimensional sex/gender concept as a theoretically grounded starting point for the operationalization of sex and gender in quantitative (environmental) health research. The iterative development process was based on gender theoretical and health science approaches and was inspired by previously published concepts or models of sex- and gender-related dimensions. The INGER sex/gender concept fulfills the four theoretically established prerequisites for comprehensively investigating sex and gender aspects in population health research: multidimensionality, variety, embodiment, and intersectionality. The theoretical foundation of INGER’s multidimensional sex/gender concept will be laid out, as well as recent sex/gender conceptualization developments in health sciences. In conclusion, by building upon the latest state of research of several disciplines, the conceptual framework will significantly contribute to integrating gender theoretical concepts into (environmental) health research, improving the validity of research and, thus, supporting the promotion of health equity in the long term.

Sulfur mustard (SM) is a chemical warfare agent leading to severe blistering of skin and mucosal surfaces, and as a long-term effect, to an increased risk for malignancies. At the molecular level, SM acts as a bifunctional alkylating agent, leading to DNA mono-adducts and di-adducts. This review is focussed on the role of poly(ADP-ribosyl)ation in the cell and tissue responses to SM-induced damage and potential role of inhibitors of poly(ADP-ribosyl)ation as therapeutic agents for SM injury.

Metal‐based antitumor agents: Halogen‐substituted titanium salane complexes showed IC50 values comparable to cisplatin. In contrast to their alkyl‐substituted congeners, they almost exclusively induced apoptotic cell death. This unique combination of very low IC50 values and pronounced preference for apoptosis makes them promising therapeutic agents.magnified image

No abstract

No abstract

DNA interstrand crosslinks (ICL) are induced both by several cytotoxic anti-cancer drugs as well as by the chemical warfare agent sulphur mustard (SM). Although measurement of ICL formation could be used in risk assessment or provide valuable predictive information on the response of malignant cells to crosslinking chemotherapeutic agents, respectively, it is currently not applied due to lack of appropriate standardized methodology. Here we describe a fast and convenient procedure for detection of ICL in human peripheral blood mononuclear cells (PBMC) as high-throughput method, termed 'reverse FADU assay'. This assay detects ICL based on the prevention of time-dependent alkaline unwinding of double-stranded DNA in a cell lysate that starts from single or double strand breaks. We have successfully established and optimized the reverse FADU assay by using human PBMC exposed to the model compounds mitomycin C, melphalan and SM. Our fully automated assay version is faster than currently used methods and possesses similar sensitivity. It operates in a 96-well format, thus allowing parallel analysis of multiple samples. Furthermore, we describe optimized protocols for sample preparation, with sample volume minimized to 100μl of blood, storage and shipment conditions. We conclude that the reverse FADU assay is an attractive candidate method for monitoring DNA damage induced by DNA crosslinking agents.

Environmental context. Many pharmaceuticals on the market have not undergone detailed evaluation for potential aquatic toxicity. We found that most tested pharmaceuticals were persistent, that phototransformation products were likely to be formed as a result of UV treatment of wastewater and that some transformation products were more toxic to bacteria than their precursor pharmaceutical compound. Thus UV treatment of wastewater does not seem appropriate to completely degrade or transform micropollutants into harmless compounds.Abstract. Data allowing for a complete environmental risk assessment of pharmaceuticals and their photoderatives in the environment are still scarce. In the present study, in vitro toxicity and both bio-and photopersistence of various pharmaceuticals (aciclovir, allopurinol, cetirizine, cimetidine, fluconazole, hydrochlorothiazide, lisinopril, phenytoin, primidone, ranitidine, sotalol, sulpiride, tramadol and valsartane) as well as their phototransformation products were evaluated in order to fill data gaps and to help prioritise them for further testing. Twelve out of the fourteen compounds investigated were found to be neither readily nor inherently biodegradable in the Organisation of Economic Cooperation and Development-biodegradability tests. The study further demonstrates that the photo-induced transformation of the pharmaceuticals was faster upon irradiation with a Hg lamp (UV light) than with a Xe lamp emitting a spectrum that mimics sunlight. Comparing the non-irradiated with the respective irradiated solutions, a higher acute and chronic toxicity against bacteria was found for the irradiated solutions of seven compounds (cetirizine, cimetidine, hydrochlorothiazide, ranitidine, sulpiride, tramadol and valsartane). No cyto-and genotoxic effects were found in human cervical (HeLa) and liver (Hep-G2) cells for any of the investigated compounds or their phototransformation products. This comparative study documents that phototransformation products can arise as a result of UV treatment of wastewater containing these pharmaceuticals. It further demonstrates that some phototransformation products may have a higher environmental risk potential than the respective parent compounds because some phototransformation products exhibited a higher bacterial toxicity.

In the present study, in vitro toxicity as well as biopersistence and photopersistence of four artificial sweeteners (acesulfame, cyclamate, saccharine, and sucralose) and five antibiotics (levofloxacin, lincomycin, linezolid, m a r b o f l o x a c i n , a n d s a r a f l o x a c i n ) a n d o f t h e i r phototransformation products (PTPs) were investigated. Furthermore, antibiotic activity was evaluated after UV irradiation and after exposure to inocula of a sewage treatment plant. The study reveals that most of the tested compounds and their PTPs were neither readily nor inherently biodegradable in the Organisation for Economic Co-operation and Development (OECD)-biodegradability tests. The study further demonstrates that PTPs are formed upon irradiation with an Hg lamp (UV light) and, to a lesser extent, upon irradiation with a Xe lamp (mimics sunlight). Comparing the nonirradiated with the corresponding irradiated solutions, a higher chronic toxicity against bacteria was found for the irradiated solutions of linezolid. Neither cytotoxicity nor genotoxicity was found in human cervical (HeLa) and liver (Hep-G2) cells for any of the investigated compounds or their PTPs. Antimicrobial activity of the tested fluoroquinolones was reduced after UV treatment, but it was not reduced after a 28-day exposure to inocula of a sewage treatment plant. This comparative study shows that PTPs can be formed as a result of UV treatment. The study further demonstrated that UV irradiation can be effective in reducing the antimicrobial activity of antibiotics, and * Marlies Bergheim