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Male rats were treated for 2 months with 1000 ppm nafenopin in the diet or for 4 or 7 days with a choline-devoid low-methionine diet. DNA was isolated from the livers and analyzed for the presence of cis-thymidine glycol-3'-phosphate (cis-dTGp) by 32P-postlabeling and for the Ievel of 8-hydroxy-deoxyguanosine (8-0H-dG) by electrochemical detection (ECD). In no DNA sample was the Ievel of cis-dTGp above the Iimit of detection of 1 modified thymidine per 106 nucleotides. With 8-0H-dG, a background Ievel of this modification of 20 8-0H-dG per 106 nucleosides was found in liver DNA of control rats, which was not affected by either treatment. It is postulated for thymidine glycol that a potential increase was below the Iimit of detection or was rapidly repaired in vivo and that the steady-state Ievel of endogenous 8-hydroxydeoxyguanosine appears not tobe influenced by the treatments chosen.
Terahertz electromagnetic fields are non-ionizing electromagnetic fields in the frequency range from 0.1 to 10 THz. Potential applications of these electromagnetic fields include the whole body scanners, which currently apply millimeter waves just below the terahertz range, but future scanners will use higher frequencies in the terahertz range. These and other applications will bring along human exposure to these fields. Up to now, only a limited number of investigations on biological effects of terahertz electromagnetic fields have been performed. Therefore, research is strongly needed to enable reliable risk assessment. Cells were exposed for 2 h, 8 h, and 24 h with different power intensities ranging from 0.04 mW/cm2 to 2 mW/cm2, representing levels below, at, and above current safety limits. Genomic damage on the chromosomal level was measured as micronucleus formation. DNA strand breaks and alkali-labile sites were quantified with the comet assay. No DNA strand breaks or alkali-labile sites were observed as a consequence of exposure to terahertz electromagnetic fields in the comet assay. The fields did not cause chromosomal damage in the form of micronucleus induction.
Two forms of a DNA polymerase have been purified from microplasmodia of Physarum polycephalum by poly(ethyleneimine) precipitation and chromatography on DEAE-Sephacel, phosphocellulose, heparin Sepharose, hydroxyapatite, DNA-agarose, blue-Sepharose. They were separated from DNA polymerase cx on phosphocellulose and from each other on heparin-Sepharose. Form HS1 enzymewas 30-40% pure and form HS2 enzyme 60% with regard toprotein contents of the preparations. Form HS2 enzymewas generated from form HS1 enzyme on prolonged standing of enzyme preparations. The DNA polymerases were obtained as complexes of a 60-kDa protein associated with either a 135-kDa (HS1) or a 110-kDa (HS2) DNA-polymerizing polypeptidein a 1:1 molar stoichiometry. The biochemical function of the 60-kDa protein remained unknown. The complexes tended to dissociate during gradient centrifugation and during partition chromatography as weil as during polyacrylamide gradient gel electrophoresis under nondenaturing conditions at high dilutions of samples. Both forms existed in plasmodia extracts, their proportions depending on several factors including those which promoted proteolysis. The DNA polymerases resembled eucaryotic DNA polymerase ß by several criteria and were functionally indistinguishable from each other. It is suggested that lower eucaryotes contain repair DNA polymerases, which are similar to those of eubacteria on a molecular mass basis.
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.
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.
In vivo covalent binding of aflatoxin metabolites isolated from animal tissue to rat-liver DNA
(1980)
Ring-labelled [\(^{14}\)C)aflatoxin B\(_1\) (AFB\(_1\)), prepared by biosynthesis. or generally labelled [\(^3\)H]AFB\(_1\) was administered by oral gavage to young adult male rats. After 6 hr. the liver was removed and two fractions were isolated, namely macromolecules, which contamed about 3 % of the initial dose of AFB\(_1\) radioactivity. and water-soluble, low-molecular aftatoxin conjugates containing about0·2% of the administered radioactivity. These two fractions were administered orally to other rats in order to determine the potential of radioactive aftatoxin residues for covalent binding to DNA. Such binding can be used as an indicator for carcinogenic potency. Liver DNA was isolated 9-12 hr after admmistration of the aflatoxin derivatives and in no case was any radioactivity detected on the DNA. It can be deduced on the basis of the limit of detection of radioactivity on the DNA, that macromolecule bound AFB\(_1\) derivatives are at least 4000 times less active than AFB\(_1\) with respect to covalent binding to rat-liver DNA. and that the water-soluble conjugates are at least 100 times less potent than AFB, itself. It is concluded that the carcinogenic risk for humans who consume liver or meat. containing such aflatoxin residues is negligible when compared with the risk from intake of aftatoxins in other food items.