Biomedical subjects

J Schulze

Publications and source records attributed to J Schulze.

At least 55 records · Page 3Linked to original sources

PubMed1999

A new method for recording surface compound potentials in sympathetic ganglia from mouse, rat, and guinea pig--application to muscarinic and nicotinic depolarizations.

We present a new method for electrophysiologic investigations in isolated autonomous ganglia of a variety of laboratory animals. This method enables determination of surface compound potentials in ganglia and changes induced by pharmacologic compounds. Advantages of our methods are as following: (1) the method is relatively simple and does not require sophisticated experimental setups, with minor modifications it is adaptable to investigate ganglia of varying sizes; (2) the signal amplitude is comparable or even higher when compared with signals obtained by other methods: (3) the apparatus allows fast addition and removal of the investigational compounds and thus the determination of acute and subacute desensitizing effects; and (4) fast preparation and minor tissue injuries during preparation of the ganglia allow determination of surface potential changes over a time period of up to 2 days without qualitative changes of the parameters. In this report we demonstrate the validity of this method using superior cervical ganglia from rat, mouse, and guinea pig. Agonists used to trigger potential changes are the cholinergic agonists acetylcholine, muscarine, nicotine, and carbachol. The possibility of receptor desensitization by these compounds is investigated by repeated application over 5 h.

Acetylcholine↗

PubMed1999

Presystemic intestinal metabolism of N-nitrosodimethylamine in mouse intestine.

N-Nitrosodimethylamine (NDMA), a common food contaminant, is a potent liver carcinogen in rodents. A high presystemic intestinal metabolism has been shown for several nitrosamines including environmentally important compounds. We determined the metabolism of 1 micron [14C]-NDMA in isolated perfused mouse intestinal segments. We found NDMA to be equally distributed between the absorbed fluid and the perfusate. During a 2-h perfusion period, 0.13% of the radioactivity was converted to CO2. The formation of CO2 was decreased by pretreatment with diallylsulfide or addition of SKF 525A, and slightly increased by phenobarbital. Hydrophilic metabolites were found in the absorbate (0.9%) and perfusate (3.8%) of untreated mice. The amount of metabolites in the absorbate was increased by treatment with acetone or phenobarbital (8-fold), but not after starvation, with formaldehyde being present only in phenobarbital-treated animals. Treatment with diallylsulfide or addition of SKF 525A reduced the amount of metabolites in acetone-treated animals to control values. In conclusion, intestinal turnover does not significantly reduce the body burden of orally ingested NDMA and thus is not a first-line defense against this carcinogenic nitrosamine. NDMA metabolism has been attributed to the presence of cytochrome P450IIE1, which has not been detected in the intestine of untreated animals. The low turnover of NDMA, the induction by acetone and phenobarbital treatment, and the inhibition by diallylsulfide suggest the presence of low amounts of this or related cytochrome P450 isozyme(s) in mouse intestine.

Animals↗

PubMed1999

[Hospital admission for bronchial asthma: comparison between inpatient children and patients attending ambulatory asthma education].

BACKGROUND: Asthma bronchiale is a chronic disease with increasing prevalence, increasing numbers of hospital admissions, and a growing mortality rate. Training courses for patients could reduce the number of in-patients, but it is still not clear what leads to an increase in admissions and whether all children have equal access to the special training courses offered. METHODS: In order to settle these questions, 40 in-patients with asthma (clinical group) were compared with a training group of 80 children of the same age, who participated in an out-patients' training course for asthmatics held at Asthma-Zentrum Rhein-Main. During a retrospective examination clinical characteristics (therapy prior to admission, number of times of seeing a doctor before admission, number of days of absence from school) and socio-economic conditions (size of flat, level of education of parents, proportion of children from families of non-German origin), as well as environmental factors (parents' tobacco smoking) were determined. FINDINGS: As expected, significant disadvantages regarding clinical characteristics and socioeconomic data were recorded for the clinical group. Children in the clinical group less often got a regular prophylactic treatment before admission to hospital (43% vs. 80%). They were absent from school three times more often than children from the training group (6 days vs. 2 days); proportionally, their parents smoked twice as often (53% vs. 23%); frequently, the number of persons living in the flat exceeded the total number of rooms (43% vs. 23%), and only 61% had their own bedroom (vs. 81% in the training group). 40% of the children in the clinical group are from families of nationalities other than German vs. only 14% in the training group. Moreover, most parents of the children in the clinical group were undereducated or had no professional training at all, and rarely held university degrees. INTERPRETATION: The results show that the patients' profiles regarding therapy and socio-economic conditions differ substantially between in-patients and children from the training group at the Asthma-Zentrum. A major part of these patients in question had no access to or could not be reached by an ambulant training course for asthmatics. Especially socially and economically disadvantaged families, and families with little compliance must be informed more carefully and should be persuaded of the benefits of ambulant training courses for asthmatics.

Adolescent↗

PubMed1998

Modulation of interleukin production by ascorbic acid.

We studied the influence of ascorbate (vitamin C) on peripheral blood mononuclear cells (PBMC) of pigs with hereditary deficiency in ascorbate synthesis. Groups of animals were depleted of, or supplemented with dietary ascorbate for up to 5 weeks. B lymphocytes and T lymphocyte subsets differed in the two experimental groups only marginally and transiently as determined by analysis of cell surface markers. The proliferative response of PBMC to B and T lymphocyte mitogens was lower in depleted as compared to supplemented animals. Interleukin (IL)-2 and IL-6 were determined by bioassays and were secreted within few hours after mitogenic activation of PBMC which contained normal physiological concentrations of ascorbate. IL-2 production peaked at about 24 h of in vitro culture after Con A activation, but it lasted for 2-3 days after PWM activation. The production of IL-2 and IL-6 were compared during systemic depletion and supplementation with ascorbate. Depleted PBMC produced IL-2 which accumulated in cultures instead of being rapidly consumed by IL-2 dependent cell growth. This suggests that cellular ascorbate influences the production of IL-2. Secretion of IL-6 by mitogen activated PBMC was also affected by prolonged dietary ascorbate depletion. The results suggest that ascorbate levels exert an early effect on immune homeostasis via reactive oxygen intermediates (ROI)-dependent expression of interleukin genes, since the transcription factor NF-kappa B is sensitive to ROI and regulates the expression of interleukin genes.

Animals↗

PubMed1998

Troglitazone, an insulin action enhancer, improves glycaemic control and insulin sensitivity in elderly type 2 diabetic patients.

The management of Type 2 diabetes mellitus with currently available oral agents may be complicated in the elderly by an increased frequency of side-effects. The effects of troglitazone, an insulin action enhancer, were studied in elderly patients with Type 2 diabetes in a double-blind, parallel-group, placebo-controlled trial. A total of 229 patients (41% male), mean age 75 (range 69-85) years, with two fasting capillary blood glucose values > or =7 and < or =15 mmol l(-1) (and within 4.0 mmol l(-1) of each other) and previously treated with either diet alone (30%) or oral hypoglycaemic agents, were randomized to placebo or troglitazone 400 mg once daily or 200 mg twice daily, or 800 mg once daily or 400 mg twice daily, for 12 weeks. After 12 weeks' treatment, fasting serum glucose was significantly lower in troglitazone-treated patients (troglitazone, adjusted geometric mean 9.4-10.4 mmol l(-1) vs placebo 12.7 mmol l(-1), p < 0.001). Adjusted geometric mean fructosamine was also lower in troglitazone-treated patients by 5 to 15% compared to placebo (P < 0.05 at all doses except 400 mg od). There was no significant difference between troglitazone doses for improvement in glycaemic control. Troglitazone lowered adjusted geometric mean fasting plasma insulin by 27-34% compared to placebo (P < 0.001) and insulin sensitivity (HOMA-S) improved by 9-15% in all troglitazone dose groups (p < 0.001). Troglitazone also lowered serum non-esterified fatty acids and triglyceride. Adverse event incidence in troglitazone-treated patients was similar to that in patients treated with placebo. No weight gain or symptomatic hypoglycaemia was recorded at any of the doses studied. Troglitazone is effective and well tolerated in elderly patients with Type 2 diabetes mellitus, providing improved glycaemic control in the absence of weight gain.

Aged↗

PubMed1998

Salmonellosis: lessons drawn from a germ-free pig model.

The germ-free pig model is shown to be useful for studying salmonellosis. The immune status of germ-free and infected gnotobiotic piglets is described. The regulatory role of cytokine is discussed and compared with our experimental findings.

Animals↗

PubMed1998

Effect of nicotine or cotinine on metabolism of 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) in isolated rat lung and liver.

The scope of the present study was to investigate whether nicotine or cotinine will affect the metabolism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in isolated perfused rat lungs and livers and to study the effect of starvation on pulmonary metabolism of NNK. NNK metabolism was investigated in isolated perfused liver and lung of male F344 rats perfused with 35 nM [5-3H]NNK in presence of a 1400-fold excess of the main tobacco alkaloid nicotine and its metabolite cotinine. In perfused rat livers, nicotine and cotinine inhibited NNK elimination and metabolism and led to a substantial increase of elimination half-life from 14.6 min in controls to 25.5 min after nicotine and 36.6 min after cotinine co-administration, respectively. In parallel, the pattern of NNK metabolites was changed by nicotine and cotinine. The pathway of alpha-hydroxylation representing the metabolic activation of NNK was decreased to 77% and 85% of control values, whereas N-oxidation of NNK and glucuronidation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) was increased 2.6- and 1.2-fold in presence of nicotine and cotinine, respectively. When isolated rat lungs were perfused with 35 nM NNK for 3 h neither the elimination nor the pattern of metabolites were substantially affected due to co-administration of 50 microM nicotine or cotinine. Cytochrome P450 2E1 is known to participate in the activation of NNK and can be induced by starvation. However, isolated rat lungs from male Sprague Dawley rats perfused with [1-14C]NNK at about 2 microM for 3 h, revealed only small differences in pulmonary elimination and pattern of NNK metabolites between fed and starved animals. These results suggest that nicotine and its main metabolite cotinine inhibit the metabolic activation of NNK predominantly in the liver whereas activation in lung, a main target organ of NNK induced carcinogenesis, remained almost unaffected.

Animals↗

PubMed1998

Cessation of insulin infusion at night-time during CSII-therapy: comparison of regular human insulin and insulin lispro.

Development of hyperglycemia with subsequent ketoacidosis is one of the potential risks of a sudden cessation of insulin delivery during continuous insulin infusion therapy with insulin pumps in patients with IDDM. To evaluate differences in the development of ketoacidosis after a sudden pump stoppage between regular human insulin and insulin lispro, we performed an open label randomized crossover investigation with 7 patients (6 male/1 female, mean age (SD: 40.9 +/- 12.9 years). At 10 p.m., 4 hours after a light dinner with a preprandial injection of the corresponding insulin, the catheter was pulled out of the skin. During the observation period, blood glucose (every hour), pH-values and base excess values (every two hours) were measured until 7 a.m. One patient, in the insulin lispro treatment arm, discontinued because early interruption criteria were met after 7 hours. With insulin lispro, the metabolic changes developed 1.5 to 2 hours earlier than with regular human insulin (after 3 hours: difference in base excess (BE) mean +/- SD: regular human insulin: -0.41 +/- 1.04 mmol/l; insulin lispro: -1.69 +/- 0.83 mmol/l, p < 0.05; blood glucose: regular human insulin: 4.93 +/- 2.87 mmol/l, insulin lispro: 8.97 +/- 3.48, p < 0.05; pH values: regular human insulin: 7.38 +/- 0.02, insulin lispro: 7.36 +/- 0.02, n.s.). In general, metabolic deterioration tended to be more pronounced with insulin lispro than with regular human insulin (deltaBE after 7 h: regular human insulin: -2.39 +/- 1.30 mmol/l; insulin lispro: -3.27 +/- 2.43 mmol/l, n.s.). In conclusion, if patients want to be treated with insulin lispro in an insulin pump, they have to be well-educated about the pharmacokinetic properties of the insulin analogue and about the possibility that ketoacidotic deterioration after an interruption of the insulin delivery may occur earlier in comparison to regular human insulin. It is anyway recommendable to perform a pump stop test when starting CSII-treatment in patients with diabetes mellitus.

Adult↗

PubMed1998

Amino acid residue 250 has a functional role in the assembly of rabbit liver microsomal cytochrome P450 2B4.

Cytochrome P450 2B4 lacking amino acids 2-27, CYP2B4 (delta2-27), was mutated at position 250 and expressed in E. coli fused to glutathione S-transferase. Expression of the E250S variant (holo- plus apoenzyme) proceeded to an extent comparable with that of CYP2B4 (delta2-27), while the protein level of the E250P mutant averaged 42% that of the control pigment. Comparison of these data with the corresponding reduced CO difference spectra of the various CYP2B4 (delta2-27) forms revealed that, in the control and E250S preparations, about 90% and 44%, respectively, of the total amount of hemoprotein present existed in the form of holoenzyme, whereas the E250P derivative failed to produce a reduced carbonyl complex. Thus, replacement of the negatively charged E250 with an uncharged, polar serine residue substantially hampered assembly of CYP2B4 (delta2-27); introduction of an alpha-helix-disrupting proline completely blocked the formation of holoenzyme. These phenomena suggested that the negative charge of E250, residing in the putative G helix, underwent pairing with some positively charged group, possibly H285 located in the I helix. Deletion of the negative charge obviously perturbed the active-site geometry such as to affect both the incorporation and/or retention of the heme ligand and the spectral binding of substrates such as hexobarbital.

Animals↗

PubMed1998

Influence of mutation of the amino-terminal signal anchor sequence of cytochrome P450 2B4 on the enzyme structure and electron transfer processes.

The role of the NH2-terminal hydrophobic patch of cytochrome P4502B4 (CYP2B4) in interactions with NADPH-cytochrome P450 reductase (P450R) and cytochrome b5 (b5) was assessed using a variant lacking the signal anchor sequence (Delta2-27). CD, second-derivative, and fluorescence emission spectra indicated that the structure of the deletion mutant slightly differed from that of the native CYP2B4. Fitting of the initial-velocity patterns for P450R- and b5-directed electron transfer to the ferric CYP2B4 forms to Michaelis-Menten kinetics revealed an approximately 2.3-fold decrease in the affinity of the two electron donors for the engineered enzyme, while the reductive efficiency remained unaffected. Circumstantial analysis suggested that impaired association of the redox proteins with P4502B4(Delta2-27) accounted for this phenomenon. Interestingly, spectral docking of P450R to the truncated pigment was not hampered, while the binding of b5 was blocked. The rates of substrate-triggered aerobic NADPH consumption in systems containing CYP2B4(Delta2-27) and P450R were 16 to 56% those obtained with the unchanged hemoprotein. Decelerated cofactor oxidation did not arise on defective substrate binding or perturbed utilization of the substrate-bound oxy complex. Experiments with b5 as the ultimate electron donor hinted at some damage to second-electron transfer to the truncated enzyme. The results are consistent with the proposal that the NH2-terminal hydrophobic region of CYP2B4 might be of importance in preservation of the catalytic competence of the enzyme.

Amino Acid Sequence↗

PubMed1998

Inhibition of protein synthesis by zinc: comparison between protein synthesis and RNA synthesis.

Inhalation of zinc fumes may lead to the acute respiratory distress syndrome. The mechanisms of pulmonary zinc toxicity are not yet understood. Therefore we investigated zinc-dependent depression of protein and RNA synthesis in rat and human lung cell lines. 1. After exposure to 120 or 150 micromol/l zinc, RNA synthesis as assessed by uridine incorporation decreased by 60-70% between 0 and 2 h exposition in rat alveolar type II cells (L2 cells) and human fibroblast-like cells (11Lu and 16Lu cells), and by 90% between 0 and 4 h in carcinoma-derived cells (A549 cells). 2. After 2 h exposure, L2, 11Lu, and 16Lu cells were half-maximally inhibited by 50 micromol/l zinc, whereas A549 cells were more resistant with half-maximal inhibition at 100 micromol/zinc. 3. Protein and RNA synthesis was inhibited in parallel in L2, 11Lu, and A549 cells as indicated by simultaneous determination of uridine and amino acid incorporation. In 16Lu cells, the decline in protein synthesis preceded RNA synthesis inhibition. Pretreatment with RNA synthesis inhibitors (amanitin or actinomycin D) had no effect on time curve and intensity of RNA synthesis inhibition. Taken together, our results indicate that the suppression of RNA and protein synthesis likely are independent phenomena, due to direct zinc effects on these biosynthetic pathways.

Amanitins↗

PubMed1998

Dependence of growth, bone metabolism and functions of polymorphonuclear leukocytes on ascorbic acid in pigs.

Pigs with hereditary ascorbate deficiency (OD pigs) were depleted of, or supplemented with, ascorbic acid by respective diets. Depletion of young (i.e. 5-7 weeks old) animals for at least three weeks had a negative effect on growth, body temperature and levels of bone alkaline phosphatase and induced symptoms of scurvy. Doses of 5 mg ascorbic acid kg-1 body weight day-1 were sufficient to reverse these effects. The level of ascorbic acid sharply decreased in plasma within one week of depletion, whereas in leukocytes it declined more slowly and to a lower extent. Bone alkaline phosphatase levels substantially declined in ascorbic acid depleted animals. Supplementation with > 100 mg ascorbic acid kg-1 body weight day-1 did not improve growth. Dietary ascorbic acid was absorbed from the intestinal lumen into the blood within less than 1 hour and reached a peak 5-6 hours after the meal. The extent of this absorption depended on the systemic ascorbic acid level. Ascorbic acid influenced leukocyte function, since the production of reactive oxygen intermediates by polymorphonuclear leukocytes decreased in supplemented animals. Thus, this animal model permits to establish the level of dietary ascorbic acid that is critical for growth of pigs as well as to study its absorption into the blood and the associated alterations in polymorphonuclear leukocytes and bone metabolism.

Alkaline Phosphatase↗

PubMed1998

[Medical guidelines for diabetes mellitus in Saxony. An instrument for interdisciplinary quality management for optimizing patient care].

Patients with diabetes still have a life expectancy of 5-10 years less and a markedly reduced quality of life than non-diabetic persons. Concepts, models, and contracts aiming at an efficient co-operative care for chronically ill patients have been developed in the new German states to overcome shortage of care. The dual care of motivated diabetic patients by family physicians and experts for metabolic diseases has proven to be efficient both in pilot studies as well as in country-wide investigations. A representative commission for diabetes has developed guidelines for such a structure of dual care. Design and content of these regional developed guidelines about an cooperative evidence based care for diabetic patients fulfills the criteria suggested by international bodies of experts and the medical society for quality assurance. The Saxonian guidelines for diabetes have been successfully implemented step by step in medical offices and hospitals. We are sure that the further implementation of the shared care system diabetes will further improve quality of care.

Adolescent↗

PubMed1997

Hepatic function in a family with a nonsense mutation (R154X) in the hepatocyte nuclear factor-4alpha/MODY1 gene.

Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic disorder characterized by autosomal dominant inheritance, onset usually before 25 yr of age, and abnormal pancreatic beta-cell function. Mutations in the hepatocyte nuclear factor(HNF)-4alpha/MODY1, glucokinase/MODY2, and HNF-1alpha/MODY3 genes can cause this form of diabetes. In contrast to the glucokinase and HNF-1alpha genes, mutations in the HNF-4alpha gene are a relatively uncommon cause of MODY, and our understanding of the MODY1 form of diabetes is based on studies of only a single family, the R-W pedigree. Here we report the identification of a second family with MODY1 and the first in which there has been a detailed characterization of hepatic function. The affected members of this family, Dresden-11, have inherited a nonsense mutation, R154X, in the HNF-4alpha gene, and are predicted to have reduced levels of this transcription factor in the tissues in which it is expressed, including pancreatic islets, liver, kidney, and intestine. Subjects with the R154X mutation exhibited a diminished insulin secretory response to oral glucose. HNF-4alpha plays a central role in tissue-specific regulation of gene expression in the liver, including the control of synthesis of proteins involved in cholesterol and lipoprotein metabolism and the coagulation cascade. Subjects with the R154X mutation, however, showed no abnormalities in lipid metabolism or coagulation except for a paradoxical 3.3-fold increase in serum lipoprotein(a) levels, nor was there any evidence of renal dysfunction in these subjects. The results suggest that MODY1 is primarily a disorder of beta-cell function.

Adult↗

PubMed1997

Clonal heterogeneity, distribution, and pathogenicity of methicillin-resistant Staphylococcus aureus.

Four thousand eighty-eight Staphylococcus aureus isolates obtained from patients hospitalised in a university clinic and four community hospitals over a period of one year were screened for methicillin resistance. A resistance rate of 5% was detected among initial isolates. Distribution of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive Staphylococcus aureus showed an increased prevalence of MRSA in clinically significant specimens such as blood, central venous catheter tips, bronchial secretions, and wound secretions. Typing of 110 MRSA strains (initial isolates) by macrorestriction analysis of chromosomal DNA revealed 26 different genotypes that could be divided into five epidemic and 21 sporadic strains. More than 50% of all isolates belonged to one type that was confirmed to be closely related to the "southern-German" epidemic strain. Production of virulence factors such as enterotoxin A-D and toxic shock syndrome-toxin 1 among MRSA strains (initial isolates) occurred in ten of 26 different MRSA types. A strong correlation between genotype and toxin production was demonstrated.

Clone Cells↗

PubMed1997

Heterogeneity in the complement-dependent bacteriolysis within the species of Borrelia burgdorferi.

Sixteen Borrelia burgdorferi strains, including all three species, were compared in a colorimetric bactericidal assay for their ability to escape the complement-dependent bacteriolysis on incubation in normal human serum free of specific antibodies (NHS). The species B. afzelii was found to be serum resistant (EB1, EB3, FEM1, FEM2, Pko), whereas strains of the species B. garinii were found to be serum sensitive (1/B29, G1, G2, PSth, PBr, PTrob). Six strains, mainly B. burgdorferi sensu stricto, were only partially sensitive (Z25, 297, B31, PKa-I, PBi). All strains activated the complement cascade in NHS, whereas only four strains (G1, G2, PBr, PSth) could activate complement in the presence of EGTA-Mg. After complement activation, covalently bound C3 fragments (C3b, iC3b) were detected on serum-sensitive as well as serum-resistant borrelial strains. Heterogeneity, however, was observed between serum-resistant and serum-sensitive strains with respect to deposition of C6 and C9. Whereas serum-sensitive strains were strongly positive for C6 and C9 and were, therefore, killed by the terminal complement complex (TCC), serum-resistant strains were devoid of C6 and C9 on their cell surface. The serum resistance may, therefore, be due to an absent or only transient formation of TCC on the bacterial surface.

Bacteriolysis↗

PubMed1997

Maturation of the mitogen responsiveness, and IL2 and IL6 production by neonatal swine leukocytes.

The maturation of the immune system of neonatal piglets was studied by following changes in the phenotypic composition and function of blood-borne leukocytes. The proportion of mature T and B lymphocytes decreased in the first week of birth and the circulating cells had poorly developed capacities to respond to mitogens and to secrete interleukins. From the end of the first week, however, there was a steady increase in the proportion of mature T cells (CD4+ and CD8+) and B cells in blood until 6-7 weeks after birth, when the study was ended. By 3-4 weeks, the relative proportions of different lymphocyte subsets resembled an adult-type composition. As they increased in prevalence, lymphocytes also developed capacities to proliferate and secrete interleukins. Proliferative responses to T-cell and B-cell mitogens reached adult levels within 2 weeks and 4-5 weeks, respectively. Blood leukocytes produced large quantities of IL6 by 1-2 weeks after birth and IL2 by 2-3 weeks. In contrast to lymphocyte patterns, the myeloid and granulocyte lineages were dominant at birth but then declined steadily. Unlike lymphocytes, the monocytes, macrophages and granulocytes appeared to be fully functional from the time of birth and exhibited a strong oxidative burst after appropriate stimulations. The magnitude of this response remained constant over the first 6-7 weeks. These results indicate that the first 3-4 weeks of post-natal life are a particularly susceptible interval for newborn piglets because constitutive and functional components necessary for specific cellular immune responses remain immature. This deficit may be offset by non-specific cellular mechanisms and maternally derived antibodies.

Animals↗

PubMed1997

Primary aromatic amines: their N-oxidative bioactivation.

There exists a diversity of pathways in mammalian cells serving to activate primary aromatic amines. 1 N-Oxidative mixed-function turnover usually involves participation of the cytochrome P450 superfamily, while catalysis by the flavin-containing monooxygenases is restricted to a few amines capable of forming imine tautomers. Surprisingly, haemoglobin metabolizes cytotoxic and carcinogenic arylamines via a monooxygenase-like mechanism, but peroxygenase activity is also operative. 2 In extrahepatic tissues that exhibit only a low level of monooxygenases, peroxidative transformations, as are brought about by prostaglandin H synthase, myeloperoxidase or lactoperoxidase, predominate in amine activation. Non-mammalian peroxidases frequently used as model systems include horseradish peroxidase and chloroperoxidase. 3 Non-enzymatic, light-induced conversion of aromatic amines to free radical or N-oxy products proceeds either via direct photolysis of the nitrogenous compounds or through attack by lipid-derived reactive intermediates generated during irradiation. 4 The interplay of the various tissue-specific processes of arylamine activation serves to explain differences in susceptibility toward the biological actions of primary aromatic amines.

Amines↗