@article{HuberLutz1984,
  author    = {Huber, K. W. and Lutz, Werner K.},
  title     = {Methylation of DNA in stomach and small intestine of rats after oral administration of methylamine and nitrite},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60984},
  year      = {1984},
  abstract  = {Young adult male Sprague-Dawley rats were given 30 \(\mu\)mol/kg body weight [\(^{14}\)C]methylamine hydrochloride and 700 \(\mu\)mol/ kg body weight sodium nilrite by oral gavage. DNA isolated from the stomach and from the first 15 cm of the smaß intestine was methylated, containing 7-methylguanine (7mG) at a level of one 7mG molecule per 5x10\8^6\) and lx10\(^7\) nucleotides, respectively. No 7mG was found fn the liver at a limit of detection of one 7mG molecule per 2xl0\(^8\) nucleotides. ln a second experiment, the excised stomachs were incubated with deoxyribonuclease before the isolation of the DNA in order to degrade DNA in the Iumen 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-methyi-N'-nitro-N-nitroso-guanidine was used to estimate the roJe 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 bot that a similar evaluation of other primary amines is required before the over-aU role of primary amine nitrosation in the etiology of human gastric cancer can be assessed.},
  subject      = {Toxikologie},
  language  = {en}
}
@article{HuberLutz1984,
  author    = {Huber, K. W. and Lutz, Werner K.},
  title     = {Methylation of DNA by incubation with methylamine and nitrite},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61011},
  year      = {1984},
  abstract  = {DNA was incubated in septum-closed 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 DN A methylation in experiments perfonned 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 nilrite 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 fonned spontaneously by nitrosation and deamination of a primary amine has a long enough lifetime to react with DNA in vitro. Using the reactioil orders established here, an extrapolation to lower concentrations found in the stomach can now be perfonned. 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.},
  subject      = {Toxikologie},
  language  = {en}
}