scholarly journals Nitrosamine-induced carcinogenesis. The alkylation of nucleic acids of the rat by N-methyl-N-nitrosourea, dimethylnitrosamine, dimethyl sulphate and methyl methanesulphonate

1968 ◽  
Vol 110 (1) ◽  
pp. 39-47 ◽  
Author(s):  
P. F. Swann ◽  
P. N. Magee

1. N[14C]-Methyl-N-nitrosourea, [14C]dimethylnitrosamine, [14C]dimethyl sulphate and [14C]methyl methanesulphonate were injected into rats, and nucleic acids were isolated from several organs after various time-intervals. Radioactivity was detected in DNA and RNA, partly in major base components and partly as the methylated base, 7-methylguanine. 2. No 7-methylguanine was detected in liver DNA from normal untreated rats. 3. The specific radioactivity of 7-methylguanine isolated from DNA prepared from rats treated with [14C]dimethylnitrosamine was virtually the same as that of the dimethylnitrosamine injected. 4. The degree of methylation of RNA and DNA produced in various organs by each compound was determined, and expressed as a percentage of guanine residues converted into 7-methylguanine. With dimethylnitrosamine both nucleic acids were considerably more highly methylated in the liver (RNA, about 1% of guanine residues methylated; DNA, about 0·6% of guanine residues methylated) than in the other organs. Kidney nucleic acids were methylated to about one-tenth of the extent of those in the liver, lung showed slightly lower values and the other organs only very low values. N-Methyl-N-nitrosourea methylated nucleic acids to about the same extent in all the organs studied, the amount being about the same as that in the kidney after treatment with dimethylnitrosamine. In each case the RNA was more highly methylated than the DNA. Methyl methanesulphonate methylated the nucleic acids in several organs to about the same extent as N-methyl-N-nitrosourea, but the DNA was more highly methylated than the RNA. Dimethyl sulphate, even in toxic doses, gave considerably less methylation than N-methyl-N-nitrosourea in all the organs studied, the greatest methylation being in the brain. 5. The rate of removal of 7-methylguanine from DNA of kidneys from rats treated with dimethylnitrosamine was compared with the rate after treatment of rats with methyl methanesulphonate. No striking difference was found. 6. The results are discussed in connexion with the organ distribution of tumours induced by the compounds under study and in relation to the possible importance of alkylation of cellular components for the induction of cancer.

2020 ◽  
Vol 1 (3) ◽  
pp. 86-97 ◽  
Author(s):  
Dorothée Ganz ◽  
Dennis Harijan ◽  
Hans-Achim Wagenknecht

Labelling of nucleic acids as biologically important cellular components is a crucial prerequisite for the visualization and understanding of biological processes.


2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ben Nie ◽  
Wei Gan ◽  
Fei Shi ◽  
Guo-Xin Hu ◽  
Lian-Guo Chen ◽  
...  

The relationship between the oxidative damage of nucleic acids and aging of animals was investigated by analyzing the nucleic acids derived from various tissue specimens of naturally aged Sprague-Dawley (SD) rats. For this purpose, we established an accurate and sensitive isotope-diluted LC-MS/MS method to determine the levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxo-dGsn) in DNA and 8-oxo-7,8-dihydroguanosine (8-oxo-Gsn) in RNA. An age-dependent increase in oxidative DNA and RNA damage was observed in the various organs examined, including the brain, liver, kidneys, and testes. Similar increases in the 8-oxo-dGsn and 8-oxo-Gsn contents were observed in three parts of the brain, the hippocampus, cerebral cortex, and cerebellum, among which, the values for the hippocampus were always the highest. When the oxidized guanosine metabolites were quantified with urine, a similar age-dependent increase was observed for both 8-oxo-dGsn and 8-oxo-Gsn. However, unlike the results of nucleic acid samples derived from the tissues, the amount of 8-oxo-Gsn was significantly higher compared to that of 8-oxo-dGsn, probably reflecting the fact that RNA degradation occurs more frequently than DNA degradation. Our finding indicates that the amount of urinary 8-oxo-Gsn could be considered as a biomarker for the sensitive measurement of oxidative stress and aging.


1969 ◽  
Vol 24 (3) ◽  
pp. 307-314 ◽  
Author(s):  
F. Dall’Acqua ◽  
S. Marciani ◽  
G. Rodighiero

The photoreaction at 3655 A between skin-photosensitizing furocoumarins and DNA leads to a photo-C4-cyclo-addition reaction in which the 5 - 6 double bond of the pyrimidine bases and the 3 -4 or the 4' -5′ double bond of the furocoumarins are involved. In continuing the research in this field, the authors have investigated the photoreactions (3655 A) of psoralen, xanthotoxin (8-methoxy-psoralen), bergapten (5-methoxy-psoralen) and 8-methyl-psoralen with native calf thymus DNA. with heat-denatured DNA and with ribosomal yeast-RNA, using labelled furocoumarins and examining also the influence of the temperature at which the irradiation was made. At room temperature (22° -30°C) psoralen photoreacts in almost equally extent with each of the three nucleic acid samples, while xanthotoxin, bergapten and 8-methyl-psoralen photoreact to a greater extent with native DNA than with denatured DNA and RNA.The temperature during the irradiation (in the range examined: 2° - 30°C) does not affect the rate of the photoreactions between the four furocoumarins and native DNA, whereas it has an evident influence on the photoreactions with denatured DNA and with RNA. In the photoreaction of psoralen this influence concerns the double bond (3 - 4 or 4' -5′) of the furocoumarin which is engaged in the C4-cycloaddition to pyrimidine bases. In the case of the other furocoumarins, the rate of the photoreactions is affected: at 2° - 8°C it is greater than at 30 °C. The preliminary formation (in the dark) of a complex between the furocoumarins and the macromolecules is involved in this temperature influence.


1968 ◽  
Vol 59 (3) ◽  
pp. 479-486 ◽  
Author(s):  
Lars-Ake Idahl ◽  
Bo Hellman

ABSTRACT The combination of enzymatic cycling and fluorometry was used for measuring glucose and glucose-6-phosphate in pancreatic β-cells from obese-hyperglycaemic mice. The glucose level of the β-cells corresponded to that of serum over a wide concentration range. In the exocrine pancreas, on the other hand, a significant barrier to glucose diffusion across the cell membranes was demonstrated. During 5 min of ischaemia, the glucose level remained practically unchanged in the β-cells while it increased in the liver and decreased in the brain. The observation that the pancreatic β-cells are characterized by a relatively low ratio of glucose-6-phosphate to glucose may be attributed to the presence of a specific glucose-6-phosphatase.


Author(s):  
Walter Ott

Descartes’s treatment of perception in the Optics, though published before the Meditations, contains a distinct account of sensory experience. The end of the chapter suggests some reasons for this oddity, but that the two accounts are distinct is difficult to deny. Descartes in the present work topples the brain image from its throne. In its place, we have two mechanisms, one purely causal, the other inferential. Where the proper sensibles are concerned, the ordination of nature suffices to explain why a given sensation is triggered on the occasion of a given brain motion. The same is true with regard to the common sensibles. But on top of this purely causal story, Descartes re-introduces his doctrine of natural geometry.


Molecules ◽  
2019 ◽  
Vol 24 (23) ◽  
pp. 4247 ◽  
Author(s):  
Rita Petrucci ◽  
Isabella Chiarotto ◽  
Leonardo Mattiello ◽  
Daniele Passeri ◽  
Marco Rossi ◽  
...  

Natural methylxanthines, caffeine, theophylline and theobromine, are widespread biologically active alkaloids in human nutrition, found mainly in beverages (coffee, tea, cocoa, energy drinks, etc.). Their detection is thus of extreme importance, and many studies are devoted to this topic. During the last decade, graphene oxide (GO) and reduced graphene oxide (RGO) gained popularity as constituents of sensors (chemical, electrochemical and biosensors) for methylxanthines. The main advantages of GO and RGO with respect to graphene are the easiness and cheapness of synthesis, the notable higher solubility in polar solvents (water, among others), and the higher reactivity towards these targets (mainly due to – interactions); one of the main disadvantages is the lower electrical conductivity, especially when using them in electrochemical sensors. Nonetheless, their use in sensors is becoming more and more common, with the obtainment of very good results in terms of selectivity and sensitivity (up to 5.4 × 10−10 mol L−1 and 1.8 × 10−9 mol L−1 for caffeine and theophylline, respectively). Moreover, the ability of GO to protect DNA and RNA from enzymatic digestion renders it one of the best candidates for biosensors based on these nucleic acids. This is an up-to-date review of the use of GO and RGO in sensors.


Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 628
Author(s):  
Dagmara Baraniak ◽  
Jerzy Boryski

This review covers studies which exploit triazole-modified nucleic acids in the range of chemistry and biology to medicine. The 1,2,3-triazole unit, which is obtained via click chemistry approach, shows valuable and unique properties. For example, it does not occur in nature, constitutes an additional pharmacophore with attractive properties being resistant to hydrolysis and other reactions at physiological pH, exhibits biological activity (i.e., antibacterial, antitumor, and antiviral), and can be considered as a rigid mimetic of amide linkage. Herein, it is presented a whole area of useful artificial compounds, from the clickable monomers and dimers to modified oligonucleotides, in the field of nucleic acids sciences. Such modifications of internucleotide linkages are designed to increase the hybridization binding affinity toward native DNA or RNA, to enhance resistance to nucleases, and to improve ability to penetrate cell membranes. The insertion of an artificial backbone is used for understanding effects of chemically modified oligonucleotides, and their potential usefulness in therapeutic applications. We describe the state-of-the-art knowledge on their implications for synthetic genes and other large modified DNA and RNA constructs including non-coding RNAs.


2020 ◽  
Vol 48 (2) ◽  
pp. 269-297
Author(s):  
Aldona Sopata ◽  
Kamil Długosz

AbstractThis article examines the acquisition of German as the weaker language in the cases of German-Polish bilingual children. Focusing on negation and verb position, phenomena that have frequently been taken as diagnostic when distinguishing between the course of language development characteristic for first (L1) and second language acquisition (L2), we analyse experimental and productive data from six simultaneously bilingual children. Due to the constrained input, German is their weaker language. The results in Forced Choice and Grammaticality Judgements tasks are compared with the results of monolingual children. We show that in the area of negation the acquisition of German as the weaker language resembles L1, and in the area of inversion and verb final position the development of the weaker language is delayed. The striking difference between bilinguals’ results in the experimental vs. productive tasks points to specific processing mechanisms in bilingual language use. In narrative contexts of the production tasks the language of the performance is activated, while the other is inhibited, which leads to a target-like performance. Structural properties of the stronger language tend to be activated, however, in the experimental tasks involving the weaker language, resulting in non-target-like responses.


1971 ◽  
Vol 34 (4) ◽  
pp. 537-543 ◽  
Author(s):  
Richard A. Lende ◽  
Wolff M. Kirsch ◽  
Ralph Druckman

✓ Cortical removals which included precentral and postcentral facial representations resulted in relief of facial pain in two patients. Because of known failures following only postcentral (SmI) ablations, these operations were designed to eliminate also the cutaneous afferent projection to the precentral gyrus (MsI) and the second somatic sensory area (SmII). In one case burning pain developed after a stroke involving the brain stem and was not improved by total fifth nerve section; prompt relief followed corticectomy and lasted until death from heart disease 20 months later. In the other case persistent steady pain that developed after fifth rhizotomy for trigeminal neuralgia proved refractory to frontal lobotomy; relief after corticectomy was immediate and has lasted 14 months. Cortical localization was established by stimulation under local anesthesia. Each removal extended up to the border of the arm representation and down to the upper border of the insula. Such a resection necessarily included SmII, and in one case responses presumably from SmII were obtained before removal. The suggestions of Biemond (1956) and Poggio and Mountcastle (1960) that SmII might be concerned with pain sensibility may be pertinent in these cases.


Agriculture ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 557
Author(s):  
Roberta Barrasso ◽  
Vincenzo Tufarelli ◽  
Edmondo Ceci ◽  
Francesco Luposella ◽  
Giancarlo Bozzo

The aim of this study was to evaluate the persistence of two signs of consciousness (rhythmic breathing and corneal reflex) in lambs slaughtered according to the traditional method and Halal ritual rite. A total of 240 lambs were examined and divided into two equal groups (n = 120 each). Lambs of group A were subjected to the stunning phase by the action of an electric current on the brain, while lambs of group B were slaughtered according to the religious Halal method without prior stunning. Rhythmic breathing (RB) and corneal reflex (CR) were used as indicators of prolonged brain function, and their evaluation was carried out by the operators in three subsequent steps at 15 s, 30 s, and 90 s post-bleeding, respectively. The stunning of the lambs reduced the animal’s state of consciousness and, consequently, reduced suffering, pain, and distress. Indeed, the lambs of group B showed longer duration consciousness than the animals stunned by electrodes. The permanence of the reflexes in Halal slaughter could be reduced by introducing a reversible stunning method to make the animal temporarily unconscious. Moreover, given that our results revealed consciousness also after 90 s post-cut, the assessment of the animal’s state of consciousness in wider time intervals than those commonly used is recommended.


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