Some Toxic Properties of Dimethylnitrosamine

Barnes, Judith; Magee, Peter

doi:10.1136/oem.11.3.167

Cited by 156 publications

(109 citation statements)

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“…Obvious damage, including nuclear changes, is present in rat liver 24 hr. after the administration of dimethylnitrosamine (Barnes & Magee, 1954), carbon tetrachloride (Cameron & Karunaratne, 1936) and beryllium (Aldridge, Barnes & Denz, 1949;Cheng, 1956). After the single doses of ethionine, fatty livers are found without any necrotic changes (Koch-Weser, Farber & Popper, 1951).…”

Section: Discussionmentioning

confidence: 99%

Diphosphopyridine nucleotide pyrophosphorylase in the nuclei isolated from poisoned and regenerating rat liver

Stirpe

Aldridge

1961

Biochemical Journal

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Section: Discussionmentioning

confidence: 99%

Diphosphopyridine nucleotide pyrophosphorylase in the nuclei isolated from poisoned and regenerating rat liver

Stirpe

Aldridge

1961

Biochemical Journal

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confidence: 93%

Toxic liver injury. The metabolism of dimethylnitrosamine

Magee

1956

Biochemical Journal

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127

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In a previous paper (Barnes & Magee, 1954) dimethylnitrosamine was shown to cause acute centrilobular necrosis of the liver in the rat, mouse, guinea pig, rabbit and dog, when given in doses of the order of 25 mg./kg. body weight. No gross abnormality was found in organs or tissues other than the liver. In long-term feeding experiments, when dimethylnitrosamine was added to the diet of rats at a level of 50 parts per million, a high incidence of malignant hepatic tumours occurred, with no evidence of primary tumours elsewhere. In similar experiments with rabbits no tumours were produced (Magee & Barnes, 1956).It appears that dimethylnitrosamine is a highly specific liver poison, and the present paper describes experiments which were performed in the hope of throwing some light on the mechanism of this specificity. A polarographic method for the estimation of dimethylnitrosamine in tissues and body fluids has been developed in this Laboratory (Heath & Jarvis, 1955) and this method was used to study the distribution of the compound in the animal body after administration, and its excretion. METHODSThe animals used were albino rats of the Porton strain, mice of the C. 57 Chester Beatty strain and commercially obtained albino mice, and cross-bred rabbits. The rats and mice were maintained on M.R.C. diet 41 (Bruce & Parkes, 1949) and the rabbits on M.R.C. diet 18 (Bruce, 1947).Dimethylnitrosamine, when given orally, was diluted with water and administered by a metal cannula attached to a syringe. For parenteral administration dilution was with 0 9 % NaCl. Intravenous injection was by tail vein in rats and by ear vein in rabbits, both procedures being without anaesthesia, unless otherwise stated. The compound was estimated in tissues and body fluids by the polarographic method of Heath & Jarvis (1955). In determinations of the total body content of dimethylnitrosamine in rats the animals were killed by intraperitoneal injection of Na pentobarbital (Veterinary Nembutal, Abbott) and immediately frozen by immersion in liquid N.. The rats were then transferred to a bucket and fragmented by percussion with a heavy brass ram-rod. The fragments were disintegrated further in 2-5% (w/v) sulphosalicylic acid by means of an Atomix blender (Measuring and Scientific Equipment Ltd., London, S.W. 1), and the resulting tissue suspension was made up to a known volume and centrifuged. Dimethylnitrosamine was estimated in a suitable portion of the supernatant fluid. A similar procedure was used for whole mice except that they were killed by cervical dislocation, and it was found possible to disintegrate them in the blender without preliminary freezing. In experiments on the excretion of dimethylnitrosamine, rats were placed in conventional metabolism cages constructed ofmetal coated with bakelite. Urine and faeces were collected separately by means of a glass separator. Total hepatectomy was performed on rats by Dr K. K. Cheng, using a two-stage technique (Cheng, 1951). The second stage of the operation on the previously prepared anim...

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“…Dimethylnitrosamine (DMN) produced haemorrhagic necrosis in the liver, haemorrhagic lesions in the lung, haemorrhagic ascites and pleural effusions in a number of animal species (Barnes and Magee, 1954). On prolonged feeding to animals, it produced tumours of the liver, kidneys and other organs (Magee and Barnes, 1962).…”

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Increased Carcinogenic Action of Dimethylnitrosamine after Prior Administration of Carbon Tetrachloride

Pound¹,

Lawson²,

Horn³

1973

Br J Cancer

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Summary.-Rats were given a single dose of dimethylnitrosamine (DMN, 20 mg/kg body weight) alone or 42 or 60 hours after a non-lethal hepatotoxic dose of carbon tetrachloride (CC14) and killed 12 months later. DMN alone produced no tumours in the kidney and a few in the liver, but when given 42 hours after CC14, tumours formed in the kidneys and the number in the liver was increased. When given after 60 hours, the incidence of kidney tumours was less but that of liver tumours was further increased. A larger dose of DMN (40 mg/kg) was tolerated 42 hours after CC14 and enhanced the number of kidney and liver tumours, the latter apparently due to an increased proportion of cholangiomata. Numerous small focal proliferations of atypical liver cells and of bile duct epithelium were observed after treatment with DMN. The incidence of these lesions in the different experimental treatments varied in a similar manner to the liver tumours.

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Some Toxic Properties of Dimethylnitrosamine

Cited by 156 publications

References 6 publications

Diphosphopyridine nucleotide pyrophosphorylase in the nuclei isolated from poisoned and regenerating rat liver

Diphosphopyridine nucleotide pyrophosphorylase in the nuclei isolated from poisoned and regenerating rat liver

Toxic liver injury. The metabolism of dimethylnitrosamine

Increased Carcinogenic Action of Dimethylnitrosamine after Prior Administration of Carbon Tetrachloride

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