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.     

Chronotropic and inotropic effects of histamine in developing chick heart: differential mechanisms before and after hatching

Chronotropic and inotropic effects of histamine were examined in isolated atrial and ventricular preparations from embryonic and hatched chicken hearts. Histamine produced positive chronotropic and inotropic responses both in embryonic and hatched hearts. The responses to histamine in middle embryonic myocardia, which were observed in the micromolar range, were antagonized by H₂ antagonists but not by H₁, H₃ antagonists and propranolol. Isobutylmethylxantine, an inhibitor of phosphodiesterase, produced a leftward shift of the concentration-response curve for the chronotropic effect of histamine in the embryo. The responses to histamine in myocardia from hatched chicks, which were observed in the milimolar range, appeared concurrently with the responses to tyramine during development and were antagonized by beta adrenoceptor antagonists but not by any of the histamine antagonists. The positive inotropic response to histamine in hatched ventricular preparations were greatly attenuated by reserpine pretreatment or in the presence of desipramine. Thus, we demonstrated that exogenously applied histamine produces positive chronotropic and inotropic responses in developing chicken hearts and that the mechanisms are different between embryonic and hatched chicks: direct action on H₂ receptors in the embryonic heart and release of norepinephrine from sympathetic nerve terminals in hatched hearts.     

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.     

肝癌特异性超抗原SEA(D227A)基因表达载体的构建与表达

目的：构建受AFP顺式作用元件调控的超抗原表达载体，将SEA(D227A)特异性的表达于AFP阳性肝癌细胞膜表面。方法：PCR扩增AFP基因启动子、增强子、linker—CD80tm和SEA(D227A)。将上述片断插入逆转录病毒载体pLXSN的多克隆位点，构建AFP基因顺式作用元件调控的肝癌特异性减毒超抗原表达载体(pLXSN SEA(D227A)—linker—CD80tm)。通过脂质体介导，以表达载体转染表达或不表达AFP的肿瘤细胞系，用RT—PCR和间接免疫荧光染色，检测SEA的表达。结果：成功地将AFP基因的启动子、增强子、linker—CD80tm和SEA(D227A)克隆到逆转录病毒载体pLXSN的多克隆位点，酶切鉴定和DNA序列分析无误，RT—PCR和间接免疫荧光法检测证实，SEA(D227A)能在AFP阳性的肝癌细胞膜特异性表达。结论：AFP顺式作用元件修饰的超抗原表达载体的构建，为下一步用其强化肝癌的免疫治疗奠定了基础。     

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.