The decomposition and toxicity of dialkylnitrosamines in rats

Heath, D. F.

doi:10.1042/bj0850417_b1d

Cited by 2 publications

(2 citation statements)

References 8 publications

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“…The lack of SSB + ALB in brain may be due to poor metabolism in brain, as seen with dimethylnitrosamine. The increase in SSB + ALB from 4 to 24 hours in liver and kidney accords with the time course of DEN metabolism, (30) and the 3-fold greater number of SSB + ALB in liver than kidney is in agreement with the 3 to 4-fold greater production of N7-ethylguanine6 (unpublished data from this laboratory). The two populations of DNA observed in kidney, one undamaged and the other damaged and repaired, may be related to the known nontarget and target cells in k i d n e~, (~,~) but such a hypothesis would require further study.…”

Section: Induction and Repair Of Ssb + Albsupporting

confidence: 80%

Target Organ Specificity: Diethylnitrosamine-and Dibenzylnitrosamine-induced Single-strand Breaks Plus Alkali-labile Bonds

Brash

Nabi

et al. 1984

Journal of the American College of Toxicology

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Quantitative dose response measurements of diethylnitrosamine-and dibenzylnitrosamineinduced DNA single-strand breaks plus alkali-labile bonds (SSB + ALB) (single-strand breaks, apurinic/apyrimidinic sites, and phosphotriesters) were performed on samples of 100,000 nuclei from Sprague-Dawley rats. Twenty-four hours after diethylnitrosamine injection, there were no SSB + ALB in brain (nontarget), SSB + ALB in kidney (target), and SSB + ALB in liver (target only after partial hepatectomy, tumor promoters, or chronic administration). Seven days after diethylnitrosamine injection, liver SSB + ALB had declined. The noncarcinogenic diethylnitrosamine analog, dibenzylnitrosamine, induced no SSB + ALB at 6 hours or 7 days postinjection. Induction of DNA damage, therefore, correlates well with target organ specificity of tumorigenesis when specificity is broadened to include those organs that exhibit tumors only when DNA damage is followed by additional treatments.

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Section: Induction and Repair Of Ssb + Albsupporting

confidence: 80%

Target Organ Specificity: Diethylnitrosamine-and Dibenzylnitrosamine-induced Single-strand Breaks Plus Alkali-labile Bonds

Brash

Nabi

et al. 1984

Journal of the American College of Toxicology

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“…Dimethylnitrosamine in doses of 50 mgfkg body weight is completely metabolized within 8-10 h in rats (Heath, 1962) and the nitrosamide, N-methyl-N-nitrosourea, is broken down at an even higher rate (Swann, 1968). Both compounds form an active alkylating intermediate which alkylates cellular components including nucleic acids and proteins; DNA and RNA are methylated predominantly on guanine to yield 7-methylguanine (Swann and Magee, 1968).…”

mentioning

confidence: 99%

Evidence of formation of N‐methyl‐N‐nitrosourea in rats given n‐methylurea and sodium nitrite

Montesano

Magee

1971

Intl Journal of Cancer

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N[14C]-methylurea and sodium nitrite were administered simultaneoussly to rats by stomach tube in order to demonstrate methylation of the nucleic acids due tojhe formation in the stomach of the corresponding nitrosamide, N[14C]-methyl-N-nitrosourea. The ion-exchange chromatograms of the hydroiysates of stomach, liver and small intestine nucleic acids show a radioactive peak corresponding to the altered base 7-methylguanine in the rat receiving N[14C]-methylurea and sodium nitrite. No evidence of 7-methylguanine was obtained when N[W]-methylurea was administered alone. These findings are interpreted as indicating that the highly potent carcinogen N-methyl-N-nitrosourea is formed in the stomach as a result of the nitrosation of the corresponding secondary amide and absorbed into the circulation of the rat. The possible consequences of the in vivo formation of carcinogenic N-nitroso compounds in the aetiology of cancer are discussed. ~~ ~ De la N[14C]-mCthylur&e et du nitrite de sodium ont &ti administris sirnultantment a des rats a I'aide d'une sonde stomacale en vue d'observer la mtthylution des acides nucliiques due a la formation duns l'estomac du nitrosamide correspondant: N[14C]-mtthyl-N-nitrosourte. Les chromatogrammes d'tchanges ioniques des hydrolysats des acides nucliiques de I'estomuc, du foie et de I'intestin grgle rivtlent un maximum radioactif qui correspond a la base 7-mithylguanine altirte chez le rat ayant

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The decomposition and toxicity of dialkylnitrosamines in rats

Cited by 2 publications

References 8 publications

Target Organ Specificity: Diethylnitrosamine-and Dibenzylnitrosamine-induced Single-strand Breaks Plus Alkali-labile Bonds

Target Organ Specificity: Diethylnitrosamine-and Dibenzylnitrosamine-induced Single-strand Breaks Plus Alkali-labile Bonds

Evidence of formation of N‐methyl‐N‐nitrosourea in rats given n‐methylurea and sodium nitrite

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