In soil, fertilizers containing inorganic nitrogen and wastes containing organic nitrogen are first decomposed to give ammonia, which is then oxidized to nitrite and nitrate. The nitrate is taken up by plants during their growth and used in the synthesis of organic nitrogenous compounds. Surplus nitrate readily moves with groundwater (2, 3). Under aerobic conditions, it percolates in large quantities into the aquifer because of the small extent to which degradation or denitrification occurs. Under anaerobic conditions, nitrate may be denitrified or degraded almost completely to nitrogen. The presence of high or low water tables, the amount of rainwater, the presence of other organic material, and other physicochemical properties are also important in determining the fate of nitrate in soil ( 4). In surface water, nitrification and denitrification may also occur, depending on the temperature and pH. The uptake of nitrate by plants, however, is responsible for most of the nitrate reduction in surface water. Nitrogen compounds are formed in the air by lightning or discharged into it from industrial processes, motor vehicles, and intensive agriculture. Nitrate is present in air primarily as nitric acid and inorganic aerosols, as well as nitrate radicals and organic gases or aerosols. These are removed by wet and dry deposition.

WHO guidelines for drinking-water quality.

The glutathione S-transferases (GST) represent a major group of detoxification enzymes. All eukaryotic species possess multiple cytosolic and membrane-bound GST isoenzymes, each of which displays distinct catalytic as well as noncatalytic binding properties: the cytosolic enzymes are encoded by at least five distantly related gene families (designated class alpha, mu, pi, sigma, and theta GST), whereas the membrane-bound enzymes, microsomal GST and leukotriene C, synthetase, are encoded by single genes and both have arisen separately from the soluble GST. Evidence suggests that the level of expression of GST is a crucial factor in determining the sensitivity of cells to a broad spectrum of toxic chemicals. In this article the biochemical functions of GST are described to show how individual isoenzymes contribute to resistance to carcinogens, antitumor drugs, environmental pollutants, and products of oxidative stress.A description of the mechanisms of transcriptional and posttranscriptional regulat...

The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance.

The immunobiology of cancer immunosurveillance and immunoediting

The biochemistry and medical significance of the flavonoids.

The emergence of tissue engineering raises new possibilities for the study of complex physiological and pathophysiological processes in vitro. Many tools are now available to create 3D tissue models in vitro, but the blueprints for what to make have been slower to arrive. We discuss here some of the 'design principles' for recreating the interwoven set of biochemical and mechanical cues in the cellular microenvironment, and the methods for implementing them. We emphasize applications that involve epithelial tissues for which 3D models could explain mechanisms of disease or aid in drug development.

Capturing complex 3D tissue physiology in vitro.

A Tandem Photochemical Approach for the Synthesis of Biologically Important Metabolites of Benzo[b]fluoranthene

The plasma membrane has been recognized as an important regulatory unit of mammalian cells during determination, differentiation, and social behaviour of individual cells within various tissues (1–4). On the molecular level, plasma membrane glycoproteins and glycolipids have been shown to be involved in these processes (1–4). Density-dependent growth of non-transformed cells in vitro has been proposed to be regulated by secreted inhibitory compounds (5–7), by the cell’s shape (8) or by diffusion boundary layers (9). On the other hand, specific cell-cell interactions via cell membrane molecules were found to be of great importance for the contact-dependent inhibition of growth (10–16) and consequently, to be responsible for the stop of growth of non-transformed cells when a confluent monolayer has been established. Several reports have shown the involvement of glycoconjugates in the control of proliferation by indirect means (11, 14, 17–19). Beyond it, a correlation between altered plasma membrane glycosylation and transformation has been demonstrated by numerous studies (20–22), and has been confirmed by DNA-transfection recently (23, 24). Furthermore, inhibitors of glycoprotein processing enzymes led to the loss of transformed phenotype of transformed fibroblasts (25, 26). These results suggest a causal relationship between glycoprotein structures and tumorigenesis.

Loss of Contact-Dependent Inhibition of Growth in Chemically Transformed Fibroblasts

A generally applicable route is reported for the synthesis of oligodeoxynucleotides which contain structurally defined N 6 -deoxyadenosine adducts, derived from sterically highly hindered dihydrodiol epoxides of polycyclic aromatic hydrocarbons (PAH).

Synthesis of Oligodeoxynucleotides Containing Diastereomeric Dihydrodiol Epoxide-N6-Deoxyadenosine Adducts of Polycyclic Aromatic Hydrocarbons.

Reaktive Metaboliten cancerogener polycyclischer Kohlenwasserstoffe: Synthese und Abfangreaktion von 9-Hydroxybenzo[a]pyren-4,5-oxid.

Different DNA-adducts produced by one given genotoxic agent can lead to different mutational preferences, as exemplified in this mini-review, by the cis-diamminedichloroplatinum(II)-induced d(GpG)-N7(1)-N7(2) adduct, giving rise predominantly to G→T transversions targeted to the 5′-modified G, the d(ApG)-N7(l)-N7(2) adduct to A→T transversions, while for the d(GpTpA)-N7(l)-N7(3) adduct no crosslink-specific mutations were observed. Expression of mutated Hras put under the control of cell-compartment specific promoters in different layers of the mouse skin showed that the consequent expression of the malignant phenotype depended on the degree of differentiation of the cell, progression to carcinomas occurring in the basal cells of the hair follicles, but not in the suprabasal layer of the epidermis. The novel Ca2+-independent protein kinase C η is expressed in differentiating and differentiated epithelial cells of the skin and was activated by cholesterol sulfate whereby tumor promotion was inhibited. Finally, the hypothesis was tested whether hypomethylation of DNA is a nongenotoxic mechanism underlying the aberrant expression of protooncogenes involved in carcinogenesis. The 5-methyleytosine content of the mouse liver tumorigenesis-relevant Hras and raf oncogenes was lower in the liver of the liver tumor-prone B6C3F1 and C3H/He mice than in the relatively resistant C57BL/6 mice, indicating that differences in DNA methylation, at least in part, account for the different susceptibilities to nongenotoxic liver carcinogens.

Franz Oesch

Papers

A Tandem Photochemical Approach for the Synthesis of Biologically Important Metabolites of Benzo[b]fluoranthene

Loss of Contact-Dependent Inhibition of Growth in Chemically Transformed Fibroblasts

Synthesis of Oligodeoxynucleotides Containing Diastereomeric Dihydrodiol Epoxide-N6-Deoxyadenosine Adducts of Polycyclic Aromatic Hydrocarbons.

Reaktive Metaboliten cancerogener polycyclischer Kohlenwasserstoffe: Synthese und Abfangreaktion von 9-Hydroxybenzo[a]pyren-4,5-oxid.

Molecular and Cellular Aspects of Chemical Carcinogenesis