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.

Analytical technique for studying the structure of glycoprotein N-glycans

The effect of trans-stilbene oxide (TSO) induction on the microsome-catalyzed binding of polycyclic aromatic hydrocarbon metabolites to DNA was investigated using two rodent species (Sprague-Dawley rat and C57BL/6N or NMRI Swiss mouse) and 2 different binding substrates (benzo[a]anthracene). It was determined that TSO exerts 2 separate effects on polycyclic aromatic hydrocarbons - it increases the rate of oxidation at the K-region of the molecule due to its induction of specific monooxygenases, and it increases the rate of deactivation of epoxide intermediates by induction of microsomal epoxide hydrolase activity. The importance of these individual effects were determined by inducing monooxygenase activity with BP, altering region specificity and inducing epoxide hydrolase (EH) activity with TSO, assessing the combined inductive effects of TSO and BP, inhibiting EH with 1,1,1-trichloropropene oxide, or increasing its activity by the addition of pure enzyme. This study shows that these effects are similar for both substrates examined, and that the effect of TSO on the binding to DNA of highly carcinogenic bay-region diol-epoxides is multi-faceted, due to its multiple inductive effects.

Modulation of the covalent binding of aryl hydrocarbon metabolites to DNA in vitro after treatment of rats and mice with trans -stilbene oxide

The oxidation of the highly tumorigenic benz[a]anthracene 3,4-dihydrodiol by rat liver dihydrodiol dehydrogenase.

The distribution of aminopyrine N-demethylase (APND), ethoxy- resorufin O-deethylase (ERRD), epoxide hydrolase (EH) and glutathione transferase (GST) activities in parenchymal (PC) and non-parenchymal (NPC) cell populations of control and Aroclor 1254-treated C57BL/6N and DBA/2N mice was determined. Furthermore, the metabolism of benzo(a)- pyrene (BP) in PC and NPC of both Aroclor 1254-treated mice strains was examined. Measurable activities of all enzymes investigated were detected in control PC as well as NPC of both mice strains; in all instances the PC possessed greater enzyme activities than did the NPC. The PC and NPC of DBA/ 2N mice had significantly lower ERRD and EH activities than PC and NPC of C57BL/6N mice. In NPC of both strains a low ratio of oxidative (APND and ERRD) to post-oxidative (EH and GST) enzyme activities was observed. Hence, NPC of C57BL/6N and DBA/2N mice might have a relatively lower ability to oxidize xenobiotics to reactive electrophiles and a greater ability to conjugate or hydrolyze those products that may be formed. Treatment with Aroclor 1254 enhanced all the enzyme activities measured in PC and NPC of both mice strains with the exception of ERRD in PC and NPC of DBA/2N mice. This is due to the fact that the induction process of ERRD by aromatic and halogenated aromatic compounds such as Aroclor 1254 depends upon the presence of a cytosolic receptor with a high affinity for this type of inducers and the DBA/2N mice have a very poor affinity receptor. After incubating BP with PC or NPC of Aroclor 1254-treated C57BL/6N mice significant amounts of 9,10-dihydrodiol, 4,5-dihydrodiol, 7,8-dihydrodiol, quinone, 9-hydroxy and 3-hydroxy derivatives of BP were detected. In contrast trace to non-detectable levels of the dihydrodiol derivatives were observed in PC as well as NPC of DBA/2N mice.

Franz Oesch

Papers

Analytical technique for studying the structure of glycoprotein N-glycans

Modulation of the covalent binding of aryl hydrocarbon metabolites to DNA in vitro after treatment of rats and mice with trans -stilbene oxide

The oxidation of the highly tumorigenic benz[a]anthracene 3,4-dihydrodiol by rat liver dihydrodiol dehydrogenase.

The distribution of carcinogen metabolizing enzymes in the mouse liver: comparison of parenchymal and non-parenchymal cell populations.

Influence of carbamazepine 10, 11-oxide on drug metabolizing enzymes