Primary and secondary amines in the human environment

Neurath, G.; Dünger, M; Pein, F.G.; Ambrosius, D.; Schreiber, Olof

doi:10.1016/s0015-6264(77)80197-1

Cited by 127 publications

(34 citation statements)

References 8 publications

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“…In the Far East, in addition to the use of tobacco and alcohol, the disease is associated with the intake of salty food and food contaminated with various mycotoxins, deficiencies in dietary vitamins and minerals, and thermal injuries due to the consumption of hot beverages. Nitrosamine carcinogens also seem to be important causative agents of esophageal SCC (3). Among these is the carcinogen, N-nitrosomethylbenzylamine (NMBA), which is present in the diet in China.…”

Section: Introductionmentioning

confidence: 99%

Chemopreventive Properties of Black Raspberries in N-Nitrosomethylbenzylamine-Induced Rat Esophageal Tumorigenesis: Down-regulation of Cyclooxygenase-2, Inducible Nitric Oxide Synthase, and c-Jun

et al. 2006

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Our laboratory has used a rodent model of human esophageal squamous cell carcinoma to identify putative chemopreventive agents for this disease and to determine their mechanisms of action. In the present study, we treated F344 rats with the esophageal carcinogen, N-nitrosomethylbenzylamine (NMBA), thrice per week for 5 weeks. Beginning 1 week later, they were fed a synthetic diet containing 5% black raspberries (BRB) for the duration of the bioassay (25 weeks). Rats were sacrificed at weeks 9, 15, and 25. Esophageal tissues were collected, and tumor data were recorded. The expression and enzymatic activities of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as well as the expression of c-Jun in the esophagi, were evaluated to investigate the mechanism(s) by which black raspberries modulate tumorigenesis. At week 25, BRB inhibited tumor multiplicity, the standard end point in this tumor model, from 3.78 F 0.41 tumors per rat in NMBAtreated animals to 2.23 F 0.21 tumors per rat in animals treated with NMBA plus BRB (P < 0.005). BRB reduced mRNA and protein expression levels of COX-2, iNOS, and c-Jun as well as the level of prostaglandin E 2 in preneoplastic lesions of the esophagus at week 25. The berries inhibited mRNA expression of iNOS and c-Jun, but not COX-2, in papillomatous lesions of the esophagus. Prostaglandin E 2 and total nitrite levels were also decreased by BRB in papillomas. These results suggest a novel tumor suppressive role of BRB through inhibition of COX-2, iNOS, and c-Jun.

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Section: Introductionmentioning

confidence: 99%

Chemopreventive Properties of Black Raspberries in N-Nitrosomethylbenzylamine-Induced Rat Esophageal Tumorigenesis: Down-regulation of Cyclooxygenase-2, Inducible Nitric Oxide Synthase, and c-Jun

et al. 2006

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“…Methylamine is by far the most widespread primary amine in the diet and is found above all in fish (9) and in vegetables (10). For this reason, and because the techniques for deter-*Abbreviations: 7mG, 7-methylguanine.…”

Section: Introductionmentioning

confidence: 99%

Methylation of DNA in stomach and small intestine of rats after oral administration of methylamine and nitrite

Huber

Lutz

1984

Carcinogenesis

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'To whom reprint requests should be sent Young adult male Sprague-Dawley rats were given 30 /xmol/kg body weight [ 14 C]methylamine hydrochloride and 700 /anol/ kg body weight sodium nitrite by oral gavage. DNA isolated from the stomach and from the first 15 cm of the small intestine was methylated, containing 7-methylguanine (7mG) at a level of one 7mG molecule per 5xlO 6 and lxlO 7 nucleotides, respectively. No 7mG was found in the liver at a limit of detection of one 7mG molecule per 2x10° nucleotides. In a second experiment, the excised stomachs were incubated with deoxyribonudease before the isolation of the DNA in order to degrade DNA in the lumen and in the uppermost lining cells. This treatment resulted in a 30% decrease in the yield of DNA and a 90% reduction in the level of 7mG formation. The results show that nitrosation of a primary alkylamine yields a precursor of an alkylating agent which has a long enough lifetime to diffuse towards and react with intracellular DNA. A correlation of DNA methylation in the stomach with the corresponding tumor formation by the methylating carcinogen N-methyl-N' -nitro-N-nitroso-guanidine was used to estimate the role of DNA damage resulting from endogenous nitrosation of dietary methylamine in man. It was concluded that the risk resulting from this single amine must be negligible but that a similar evaluation of other primary amines is required before the over-all role of primary amine nitrosation in the etiology of human gastric cancer can be assessed.

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“…The generation of nitrosamines from amines and nitrite under acidic conditions could represent an important mechanism for the formation of carcinogens in the stomach (1) from ubiquitous dietary amines (2) and unavoidable salivary nitrite (3,4). With primary amines, chemically unstable products are formed which react readily with nucleophiles.…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless it seemed important to investigate a DNA damage exerted by the nitrosation products of methylamine, a dietary constituent of fish (5) and vegetables (2). Since the chemistry predicted the formation of a methylating agent (6), methylated DNA bases were searched using techniques established in earlier work with dimethylamine (7).…”

Section: Introductionmentioning

confidence: 99%

Methylation of DNA by incubation with methylamine and nitrite

Huber

Lutz

1984

Carcinogenesis

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'To whom reprint requests should be sent DNA was incubated in septum-dosed reaction vials with [14 C]methylamine and nitrite. The DNA was purified, hydrolysed with hydrochloric acid, and the purines were analysed by h.p.l.c. 7-Methylguanine was detectable as a result of DNA methylation in experiments performed in 100 mM acetate at pH 4. Using different concentrations of amine and nitrite a first order reaction for total amine and a second order for total nitrite could be shown. A study on the pH dependence using 100 mM malonate buffer, pH 2.0 -6.0, revealed a maximum rate at pH 3.5, with steep slopes above and below this pH value, in agreement with a mathematical analysis of the reaction equations. The data show that the alkylating agent formed spontaneously by nitrosation and deamination of a primary amine has a long enough lifetime to react with DNA in vitro. Using the reaction orders established here, an extrapolation to lower concentrations found in the stomach can now be performed. Future in vivo experiments on the methylation of gastro-intestinal DNA then would show to what extent DNA in a cell is protected from alkylation.

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Primary and secondary amines in the human environment

Cited by 127 publications

References 8 publications

Chemopreventive Properties of Black Raspberries in N-Nitrosomethylbenzylamine-Induced Rat Esophageal Tumorigenesis: Down-regulation of Cyclooxygenase-2, Inducible Nitric Oxide Synthase, and c-Jun

Chemopreventive Properties of Black Raspberries in N-Nitrosomethylbenzylamine-Induced Rat Esophageal Tumorigenesis: Down-regulation of Cyclooxygenase-2, Inducible Nitric Oxide Synthase, and c-Jun

Methylation of DNA in stomach and small intestine of rats after oral administration of methylamine and nitrite

Methylation of DNA by incubation with methylamine and nitrite

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