Evidence for specific lead-delta-aminolevulinate complex formation by carbon-13 nuclear magnetic resonance spectroscopy.
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Biomedical subjects
Publications and source records attributed to C S Baxter.
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Radiomethyl incorporation in vitro into Nepsilon-methyllysine of histones from rat liver nuclei incubated in the presence of S-adenosyl[methyl-3H]methionine is stimulated if the polycations polylysines, protamines, or histones are added to the incubation mixture. Maximal stimulation occurs at a cation/nucleotide ratio of 0.5. Past this point stimulation drops, except in the case of very lysine-rich histone H-1, for which the maximal level of incorporation remains constant upon further addition of this histone. Bio-Gel P-10 chromatography, differential precipitation, and gel electrophoresis of radiomethylated histones indicate that although the usual incorporation of radiomethyl into histone H-3 is not affected, active methylation of H-1 occurs in the presence of polycations. Column chromatographic amino acid analysis reveals that the methylation of H-1 will specifically generate Nepsilon-monomethyllysine. Except for this condition, H-1 is never methylated in vivo or in incubated cell nuclei. Because H-1 is the weakest bound histone in chromatin, the above phenomena may be explained by assuming that, within the chromatin, polycations displace the lysine-rich histone towards the nucleosome, which results in its abberant methylation, assuming that the native nucleosome is the seat of the histone lysine methyltransferase.
Linear alkanes of specific chain length between 6 and 16 carbon atoms, an aryl derivative of dodecane, and a phorbol diester were tested in a cell culture system for relative ability to enhance mutagenesis induced by a chemical carcinogen, methylazoxymethanol acetate (MAM). Mutation frequencies at the ouabain-resistance locus were measured. Results indicated an excellent correlation between the relative activities of the above compounds in enhancing mutagenesis in the in vitro culture system and their tumor-promoting activities in mouse skin. None of the compounds tested showed mutagenic activity per se, further lending support to the theory that promoters act via derepression of latent carcinogen-induced damage to the genome.
The incidence of myocardial infarction and the return to work for survivors were studied among the employees of an English car assembly plant by analysing 12 811 medical records of persons employed during the seven years between January 1966 and December 1972. The standardized morbidity ratio of myocardial infarction found in this study calculated on the basis of incidence rates reported by Kinlen )1973) for the Oxford community in which the factory was situated was 90. The standardized morbidity ratio from production line workers only was 66 and that for the monthly paid staff 272. Of the production line workers who survived the attack 22 (90%) returned to their previous jobs without undue difficulty and with two exceptions within four months of the onset of their illness; there was no relation between length of absence and age at the time of attack. These findings suggest that workers in mass production jobs such as car assembly are not special risk from myocardial infarction, and most of those who survive a heart attack are able to return to their former work. Taken with Kinlen's (1973) study and that of Armstrong et al. (1972) in Edinburgh, they also bear out mortality data by indicating that in Oxfordshire the incidence of coronary heart disease is lower than the British average.
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The alkaline elution assay was used to monitor DNA single-strand breaks in embryonic tissue following exposure to the DNA-damaging teratogen N-methyl-N-nitrosourea (MNU, CAS No. 694-93-5). An animal model was developed in which nearly every fetus exposed to the highest dose of MNU had malformations of the hindlimbs while the fetuses exposed to the lowest dose of MNU had none. Hindlimbs pooled within litters were analyzed for DNA single-strand breaks by alkaline elution conducted at rapid (0.35 ml/min) and slow (0.35 ml/min) speeds. Breaks in the DNA of hindlimbs exposed to teratogenic doses of MNU were readily detected by alkaline elution only if slower speeds were used in the assay. Using the more sensitive procedure, DNA breakage was monitored over a 24-h period. DNA breakage peaked in the MNU-exposed hindlimbs in a dose-dependent manner 4 h after injection. While the elution profiles of hindlimbs exposed to the lower doses of MNU returned to control levels 8 h after injection, single-strand breaks persisted in the hindlimbs exposed to the highest dose of MNU for at least 20 h. These latter data suggest that the highly teratogenic dose of MNU induced DNA damage that was more slowly repaired than that produced at lower doses, possibly by saturation of DNA repair systems. Although some necrosis did occur in hindlimbs exposed at teratogenic dose levels, it was not severe and it did not appear to influence the alkaline elution results. These experiments show that alkaline elution is a sensitive assay for the detection of DNA damage in embryonic tissues.