Dietrich, Daniel R.
0000-0003-0416-3811 Berufsbeschreibung
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Application of laser-capture microdissection to study renal carcinogenesis
Kidney cancer is characterized by significant morphological and molecular heterogeneity. Evaluation of mechanisms involved in the development and progression of kidney cancer require comprehensive analyses of genomes, transcriptomes, proteomes, and methylation profiles in normal and tumor tissue. To date, indiscriminate homogenates of tumor tissue or biopsy samples have been used as a source for DNA, RNA, or protein isolation. A major technical improvement has been the development of laser-assisted microdissection that allows the isolation of morphologically similar cells. The applications of this technology to kidney cancer research are outlined.
Risk Assessment Workgroup Report
The Risk Assessment Work Group focused on six charge questions related to CHABS, cyanobacteria and their toxins. The charge questions covered the following topics: Research needed to reduce uncertainty in establishing health based guidelines. Research that minimize the cost and maximize the benefits of various regulatory approaches. Exposure pathways for receptors of concern. Data available to support the derivation of health-based guideline values for harmful cyanobacterial algal blooms. Ecological services that guidelines or regulations should protect? A framework for making risk management determinations that incorporates consideration of the characteristics of CHABs, the risk for human health, ecosystem viability, and the costs and benefits of CHABs detection and management? The Work Group concluded that there is a considerable amount of human case-study data and information from animal studies to demonstrate that cyanobacterial toxins pose a hazard to humans, domestic animals, wildlife, and the ecosystem. However, the data on dose-response are limited and confounded by a lack of sufficient pure toxin to conduct most of the toxicological studies that will be needed in order to answer remaining questions on risk, and to provide the data for quantitative dose-response analysis. The Work Group recommended that research on purification or synthesis of pure toxin must be accomplished before the large scale studies to establish dose-response relationships will be possible. As the necessary-pure toxins become available, the Work Group recommended that studies be prioritized by the impact that they will have on reducing the uncertainty in the risk assessment in order to minimize the research costs and maximize the risk assessment benefits. Use of quantitative structure activity relationships (QSAR) and toxicity equivalency factor studies are also recommended as approaches for filling dose-response data gaps. The Work Group recognized that CHABs rarely introduce single toxins into the water supply. Under CHAB conditions, affected water is likely to contain a variety of toxins in varying concentrations that may change over the duration of the bloom. Accordingly, research on cyanotoxin interactions is needed, along with the development of risk assessment approaches for CHAB mixtures. The development of simple, accurate analytical methods that can be utilized by most analytical laboratories or used in the field was recognized as a major data need for establishing exposure potential and monitoring bloom conditions. Most currently available methods are time-consuming and/or costly. Human exposure to cyanobacterial toxins can occur through ingestion of contaminated drinking water, plus dermal contact and/or inhalation of aerosols while bathing and showering in tap water. Treatment can reduce the concentrations of both the toxins and the bacteria in the treated water but there is still much to be learned about the effectiveness of most treatment technologies on cyanobacteria and toxin removal. Human exposure to cyanobacteria and their toxins also occurs through incidental ingestion, dermal contact, and inhalation of aerosols during recreational use of surface waters, ingestion of contaminated fish and other foods of aquatic origin, and/or BGAS supplements. Establishing intakes and duration parameters for these exposure scenarios will facilitate the application of risk assessment approaches to these situations.
Lack of Estrogenic and Endocrine Disrupting Effects in Juvenile Rainbow Trout Exposed to a New Zealand Pulp and Paper Mill Effluent
Previous studies have noted effects of pulp and paper effluents on the physiology of fishes including; smaller gonads, increased age to maturation, alterations in secondary sex characteristics, reduced plasma sex steroid levels, and the induction of vitellogenin (Vtg) in males and juveniles. A program to determine the potential impacts of a modem New Zealand pulp and paper mill effluent on fishes employed a combination of long- and short-term exposures of the juvenile (1+) rainbow trout, Oncorhynchus mykiss, to the effluent. Juvenile (1 + aged) rainbow trout were exposed to a mixed thermomechanical pulp/bleached kraft (TMP/BK) mill effluent at a range of concentrations from environmentally relevant (10%) to 70% (effluent by volume) in three exposure studies. During 21-,56- and 320-day exposures to 10% and 30% (v/v) effluent, no significant impacts on circulating testosterone, and pregnenolone levels were observed. No significant induction of liver MFO activity was observed at any exposure concentration. Vitellogenin induction or expression of the estrogen receptor in juvenile males was not observed in fish from either experiment. High experimental mortality was observed in fish exposed to 70% (v/v) secondary treated effluent compared to a reference treatment during the 2l-d exposure and was linked to an atypically high suspended solids load. Thus, the combined data from these experiments demonstrated a lack of estrogenicity or impacts on steroidogenesis following exposure to TMP/BK mill effluent. However, a parallel experiment using sexually mature rainbow trout did show elevated Vtg in males. Thus, the presence of estrogenic compounds cannot be ruled out, but appears to be infrequent. Results from parallel studies with mosquitofish have shown androgenic activity in the effluent under investigation.