Biomonitoring of aromatic amines and alkylating agents by measuring hemoglobin adducts

Summary Analysis of hemoglobin adducts in blood samples is suitable for the biological monitoring of genotoxic chemicals. The method is specific because the compound to which the individual was exposed is identified. The sensitivity of the method depends on the analytical procedure applied, but is hardly limiting since large amounts of the protein can be obtained. The method provides not only information about the internal exposure to the environmental chemical, but also about the individual's capacity to generate ultimate genotoxic metabolites from it. Since macromolecular damage in blood cells is correlated to that in potential target tissues, this information is relevant to risk assessment, insofar as macromolecular damage produced by a specific chemical can be correlated with the development of tumors.     

Heterocyclic amines: evaluation of their role in diet associated human cancer

1 Heterocyclic amines are formed in parts per billion levels when meat is cooked.
2 The heterocyclic amines MeIQx and PhIP are efficiently absorbed into the systemic circulation after ingestion of cooked food.
3 We have shown that MeIQx and PhIP, both in vitro and in vivo , are substrates for human hepatic CYP1A2, which exclusively and efficiently catalyses their conversion to genotoxic hydroxylamines.
4 MeIQx and PhIP are promutagens. MeIQx is a very powerful bacterial mutagen whereas PhIP is a more potent mammalian cell mutagen. Using a mammalian cell target gene, hprt , we have shown that PhIP induces a characteristic mutational 'fingerprint'.
5 MeIQx and PhIP are carcinogenic in bioassays. The PhIP mutational 'fingerprint' has been detected in the Apc gene of 5/8 colonic tumours induced by PhIP in rats.     

Stress-induced changes in behavior and function of the neurohormonal systems in monkeys differing in social rank

Research Institute of Experimental Pathology and Therapy, Sukhumi. (Presented by Academician of the Russian Academy of Medical Sciences B. A. Lapin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 114, No. 11, pp. 457–459, November, 1992.     

Probing the regioselective C‐deuteriation of lithium enolates derived from 2‐methyl‐tetralone in the presence of substituted tertiary amines

Results are reported on the regioselective C‐deuteriation of 2‐methyl‐tetralone using a series of D‐sources and tertiary amines as potential mediators. The results presented further aid the understanding of kinetic deuteriation of both ‘base‐containing’ and ‘base‐free’ enolates. Copyright © 2006 John Wiley & Sons, Ltd.     

Development of acute autoimmune encephalomyelitis in mice: Factors regulating the effector phase of the disease

The development of acute experimental autoimmune encephalomyelitis (EAE) in mice is potentiated by the use of Bordetella pertussis vaccine as an adjuvant. Histamine sensitizing factor (HSF) extracted from B. pertussis is the active adjuvant agent and causes a mild increase in cerebrovascular permeability. During the development of EAE, there is an additional increase in vascular permeability of the brain and spinal cord. The adjuvant action of B. pertussis HSF does not appear to mimic a generalized beta-adrenergic blockade, since the course of EAE is not potentiated by adrenalectomy. The cerebrovascular permeability changes observed in EAE are probably mediated by vasoactive amines, since the expression of EAE can be blocked by vasoactive amine antagonists.     

Effects of chlorpromazine on hypothalamic aminergic neurons and stress responses in moderate cold

Summary Guinea-pigs were treated with chlorpromazine or 0.9% NaCl and exposed to +4° C or +23° C for 2 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5HT), 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum and urinary catecholamines, muscle and liver glycogen and blood glucose were also measured. Chlorpromazine caused deep hypothermia at this moderately cold temperature and slight hypothermia at room temperature. Cold increased the activity of noradrenergic and serotonergic neurons, as indicated by the increase in hypothalamic MHPG and 5-HIAA and also the MHPG∶NA and 5-HIAA∶5-HT ratios. A tendency towards drug-induced inhibition of hypothalamic serotonergic neurons was seen, although this was not significant. A drug-induced inhibition of noradrenergic neurons could not be ruled out. Increased drug-induced turnover of DA was observed in the cold, and a tendency in the same direction was seen at room temperature. Excretion of DA into the urine was induced by chlorpromazine. The hypothermic guinea-pigs had low serum catecholamines, indicating diminished sympathetic activity, but high urinary catechols, a sign of cold stress.     

Gastric mucosal protection with β-phenylethylamine (PEA) and other sympathomimetic amines against absolute ethanol in the rat

The purpose of this study was to investigate the potential of -phenylethylamine (PEA), an amphetamine-like compound present in the blood during high stress situations, to protect rat gastric mucosa against absolute ethanol. F-344 rats were pretreated with PEA in saline at several dose levels and at various times prior to oral administration of 1 ml absolute ethanol. PEA at dose levels of 50 and 100 mg/kg significantly reduced the severity of alcohol-induced lesions following oral, but not parenteral, treatment. The duration of protection with PEA was approximately 90 min, with maximum protection observed when PEA was administered 15–30 min before alcohol. Pretreatment with indomethacin did not prevent or reduce the protection induced by PEA. Other sympathomimetic amines such as isoproterenol and ephedrin were similarly cytoprotective against absolute ethanol while amphetamine, phenylephrine, and epinephrine proved ineffective. These results add further support to the role of the sympathetic nervous system in regulating gastric mucosal protection in the rat.     

Biological monitoring of occupational exposure to toluene diisocyanate

Summary The study validated the use of urinary toluene diamine (TDA) in postshift samples as an indicator of preceding 8-h exposure to toluene diisocyanate (TDI). Nine workers exposed in TDI-based polyurethane foam production were studied. Their exposure levels varied in 8-h time-averaged samples from 9.5 to 94 g/m³. The urinary TDA concentrations varied from 6.5 to 31.7g/g creatinine and they were linearly related to the atmospheric TDI levels. Approximately 20% of TDI is metabolized to diamines but their specificity is remarkable to the extent that by analysis for the 2,4- and 2,6-diamino isomers an idea of the percutaneous absorption may be had.     

Regional alterations of brain biogenic amines and GABA/glutamate levels in rats following chronic lead exposure during neonatal development

Wistar rat pups were administered either a high dose of lead acetate (400 g lead/g body weight/day) or a low dose (100 g lead/g body weight/day) by gastric intubation, from 2 days through 60 days of age. The rats on both these doses exhibited statistically significant decreases in body and brain weights throughout the lead treatment period. A group of rats on high dose was also rehabilitated by discontinuing the lead from 60 days of age. In these rats, at 160 days of age, the body weight but not the brain weight recovered to normal levels. During the lead intake, the rats on high dose revealed significant elevations in the levels of noradrenaline (NA) in the hippocampus (HI), cerebellum (CE), hypothalamus (HY), brainstem (BS), and accumbens-striatum (SA). The elevated levels in all the above regions except in the HY persisted even after rehabilitation. The dopamine (DA) levels changed significantly in opposite directions in HY (elevation) and BS (reduction) during the lead treatment, and the HY recovered after rehabilitation. Under lead, the serotonin (5HT) levels were elevated significantly in the HI, BS and MC (motor cortex), while after rehabilitation the abnormality persisted only in the MC. Low dose lead treatment was also effective on the same areas of brain. In the low dose group, estimation of the levels of GABA and glutamate were also done, and a significant decrease of GABA in CE and glutamate in MC was observed. The differences observed in the neurotoxic effects (none or significant) of lead in the different regions for each of the transmitters (NA, DA, 5HT) supports the interesting conclusion that the vulnerability of the axon terminals of any given type is dependent on some regional factors, although the projections of the different regions originate from an apparently similar category of neurons in the brain stem.     

Tumors of the urinary bladder in painters: a case-control study

In a case-control study, 403 male patients with a diagnosis of "bladder tumor" and (as controls) 426 patients suffering from prostate disease were investigated. The results of this study indicate that past employment as a painter was associated with an excess risk of bladder tumor. The relative risk of bladder tumor estimated for painters was 2.76. The possible role of benzidine-based azodyes (or azodyes based on substituted benzidines) as a carcinogenic risk factor for painters is discussed.