[A critical assessment of phytotherapy for prostate cancer]. / Eine kritische Bewertung der Phytotherapie des Prostatakarzinoms.

Prostate cancer patients increasingly use complementary and alternative medicines to support the body's immune system in addition to conventional treatment to minimize morbidity associated with conventional treatment, to enhance the quality of life, and ultimately in the hope to cure cancer when conventional treatment fails. As there is a large variety of phytomedicines promoted as potential treatment for prostate cancer, the aim of this review was to differentiate between preventive and therapeutic approaches and evaluate which phytochemicals might be suited for therapy of prostate cancer. Therefore, preclinical in vitro and in vivo data as well as clinical trials with phytosubstances such as genistein, lycopene, epigallocatechin gallate, resveratrol, and mistletoe were assessed. The presented data show that at present there is no clinical evidence that phytochemicals might have a therapeutic use in prostate cancer in relation to reduction of tumor progression or improved survival. The question about an improved immune function or quality of life remains open. Potentially the use of phytochemicals could play a role in a preventive setting.

Soy isoflavone genistein in prevention and treatment of prostate cancer.

Dietary habits and incidence of prostate cancer (PCa) are very different in several parts of the world. Among the differences between Eastern and Western diets is the greater intake of soy in the Eastern cultures. This might be one factor contributing to a lower incidence of PCa in Asian men. Many studies using PCa cells and animal studies of chemical carcinogenesis have shown that a wide range of dietary compounds have cancer chemopreventive potential. Therefore, the interest in nutrition-based approaches for prevention and treatment of PCa is increasing. We reviewed all experimental preclinical in vitro and in vivo data as well as clinical trials performed with soy isoflavone genistein for prevention and treatment of PCa. The preclinical data for genistein presented in this review show a remarkable efficacy against PCa cells in vitro with molecular targets ranging from cell cycle regulation to induction of apoptosis. In addition, seemingly well-conducted animal experiments support the belief that genistein might have a clinical activity in human cancer therapy. However, it is difficult to make definite statements or conclusions on clinical efficacy of genistein because of the great variability and differences of the study designs, small patient numbers, short treatment duration and lack of a standardized drug formulation. Although some results from these genistein studies seem encouraging, reliable or long-term data on tumor recurrence, disease progression and survival are unknown. The presented data potentially allow recommending patients the use of genistein as in soy products in a preventive setting. However, at present there is no convincing clinical proof or evidence that genistein might be useful in PCa therapy.

Conversion of adamsite (phenarsarzin chloride) by fungal manganese peroxidase.

Fungal manganese peroxidase was found to convert the persistent chemical warfare agent adamsite (phenarsarzin chloride) in a cell-free reaction mixture containing sodium malonate, Mn(2+) ions, and reduced glutathione. The organo-arsenical compound disappeared completely within 48 h accompanied by the formation of a more polar metabolite with a clearly modified UV spectrum. Thus, As(III) in the adamsite molecule was oxidized by manganese peroxidase to As(V) which added dioxygen and released chloride.

Anaerobic incorporation of the radiolabeled explosive TNT and metabolites into the organic soil matrix of contaminated soil after different treatment procedures.

Four bioreactor designs were performed to evaluate the level of incorporation of 14C-labeled 2,4,6-trinitrotoluene (TNT) and metabolites into the organic soil matrix of different anaerobically treated contaminated soils. The contaminated soils were amended with molasses slivers (80:20% per weight) as auxiliary substrate to enhance microbial activity. After 5 weeks (bioreactors 1 and 2), 8 weeks (bioreactor 3) and 12 weeks (bioreactor 4) of anaerobic incubation, we determined 41%, 58%, 72%, and 54%, respectively, of the initially applied radioactivity immobilized in various soil fractions. After alkaline hydrolyses of the solvent-extracted soils, low quantities of radiolabel were found in the humic and fulvic acid fractions, whereas the bulk of 14C activity was found to be strongly bound to the humin fraction (solid soil residues). The amounts of solvent extractable radioactivity were 53%, 40%, 16%, and 29% for bioreactors 1, 2, 3, and 4, respectively. The level of TNT transformation at the end of the experiments was within 90-94%. Regarding the results presented in this study, we can assume that there is the possibility of high incorporation levels of TNT metabolites into the soil organic matrix mediated by microbial cometabolism under strictly anoxic conditions.

Identification of oxidized TNT metabolites in soil samples of a former ammunition plant.

Water extracts of soil samples of the former ammunition plant "Tanne" near Clausthal-Zellerfeld, Lower Saxony, Germany, were investigated for highly polar oxidized 2,4,6-trinitrotoluene (TNT) metabolites. 0.4 to 9.0 mg/kg dry soil 2,4,6-trinitrobenzoic acid (TNBA) and 5.8 to 544 mg/kg dry soil 2-amino-4,6-dinitrobenzoic acid (2-ADNBA) were found. In addition to the oxidized metabolites, TNT, 4- and 2-aminodinitrotoluene (4- and 2-ADNT), and 2,4-dinitrotoluene (2,4-DNT) were extractable with water. Most interestingly, in one sample, 2-ADNBA represented the main contaminant. The origin of the oxidized nitroaromatics is unknown at this time. They might be generated chemically or photochemically. Furthermore, a biological synthesis seems possible.

Mass balance studies with 14C-labeled 2,4,6-trinitrotoluene (TNT) mediated by an Anaerobic desulfovibrio species and an Aerobic serratia species.

Investigations were carried out to evaluate the level of incorporation of radiolabeled 2,4,6-trinitrotoluene (TNT) and metabolites into the bacterial biomass of two different bacterial species after cometabolically mediated TNT transformation. Biotransformation experiments with 14C-TNT indicated that TNT was not mineralized; however, carbon derived from TNT became associated with the cells. It was found that more than 42% of the initially applied radiolabel was associated with the cell biomass after cometabolic 14C-TNT transformation with the strictly anerobic Desulfovibrio species strain SHV, whereas with the strictly aerobic Serratia plymuthica species strain B7, 32% of cell-associated 14C activity was measured. The remainder of the radiolabel was present in the supernatants of the liquid cultures in the form of different TNT metabolites. Under anoxic conditions with the Desulfovibrio species, TNT was ultimately transformed to 2,4,6-triaminotoluene (TAT) and both diaminonitrotoluene isomers, whereas under oxic conditions with the Serratia species, TNT was converted to hydroxylaminodinitrotoluenes and aminodinitrotoluenes, with 4-amino-2,6-dinitrotoluene (4ADNT) being the major end product. In both culture supernatants, small amounts of very polar, radiolabeled, but unidentified metabolites were detected. At the end of the experiments approximately 92% and 96% of the originally applied radioactivity was recovered in the studies with the Serratia and Desulfovibrio species, respectively.

Highly polar metabolites of nitroaromatic compounds in ammunition wastewater.

Transformation processes of nitroaromatic compounds (NAC) are described that lead to polar and highly hydrophilic metabolites in ammunition waste water. For the identification of proposed metabolites, several analytical methods for the separation and determination of these compounds were developed and applied to the investigation of a former ammunition plant and its surroundings. The compound classes which were investigated include nitro and amino substituted toluenesulfonic acids, nitrobenzoic acids, aminobenzoic acids and nitromethylphenols. Method development was usually done with high performance liquid chromatography and ion pairing or ion suppression techniques. In the leachate water of a disposal site of a former ammunition plant in Stadtallendorf, Germany, 15 compounds from the above-mentioned categories have been found to be present in concentrations up to a few hundred microgram/L. The presence of so many polar compounds suggest that current and future surveying programs should include representative analytes of the investigated categories.

Gas chromatographic determination of aromatic amines in water samples after solid-phase extraction and derivatization with iodine. I. Derivatization.

A new method for the selective determination of aromatic amines is presented, which is based on the solid-phase extraction at pH 9 and subsequent derivatization of the analytes to the corresponding iodobenzenes. These can selectively and sensitively be determined with gas chromatography and electron-capture detection. Separation of at least 30 compounds in a single chromatographic run in 30 min is possible. With this method, 56 aromatic amines were investigated, and only in six cases no derivatives were obtained. Limits of quantitation were between 0.5 and 8 micrograms 1(-1), but may still be lowered with higher sample volumes or different injection techniques. The application to water samples revealed the suitability for the investigation of ground, leachate and wastewater.

Gas chromatographic determination of aromatic amines in water samples after solid-phase extraction and derivatization with iodine. II. Enrichment.

A procedure for the enrichment of aromatic amines via solid-phase extraction was developed. A HR-P phase based on styrene-divinylbenzene was used for the investigations, generally followed by derivatization with iodine and determination via GC-ECD. The recoveries of 53 aromatic amines in a drinking water matrix at pH 9 were determined. Most anilines showed relative recoveries between 80-120% with relative standard deviations of< or = 5% at concentration levels between 10 and 20 micrograms 1(-1). The comparison with a wastewater matrix led to similar results. The enrichment procedure was applied to real samples, e.g., samples of ammunition wastewater.

Microbial transformation of 2,4,6-trinitrotoluene in aerobic soil columns.

2,4,6-Trinitrotoluene (TNT)-contaminated soil material of a former TNT production plant was percolated aerobically in soil columns. Nineteen days of percolation with a potassium phosphate buffer supplemented with glucose or glucose plus ammonium sulfate caused an over 90% decline in the amount of extractable nitroaromatics in soils containing 70 to 2,100 mg of TNT per kg (dry weight). In the percolation solution, a complete elimination of TNT was achieved. Mutagenicity and soil toxicity were significantly reduced by the percolation process. 4-N-Acetylamino-2-amino-6-nitrotoluene was generated in soil and percolation fluid as a labile TNT metabolite.

Bioremediation of 2,4,6-trinitrotoluene-contaminated soils by two different aerated compost systems.

Two composting systems were compared on a laboratory scale as a bioremediation technology for degradation or immobilization of 2,4,6-trinitrotoluene (TNT) in contaminated soils. The first compost was aerated from the beginning whereas the second compost was only aerated after an anaerobic prephase of 65 days. In the first compost system the TNT concentration declined rapidly by 92% but, at the end, TNT could be partially recovered. During the anaerobic prephase of the second compost system, TNT was almost completely converted to aminodinitrotoluenes, which during the subsequent aeration almost entirely disappeared. In addition, the second compost generated less toxic material than the first one as confirmed by inhibition of bioluminescence of Vibrio fischeri. These data show that microbiological TNT-degradation systems can be successfully designed which are prerequisite for an efficient bioremediation of contaminated soils.