Some Studies on the Action of Urethane on Mice

Pn, Cowen

doi:10.1038/bjc.1947.39

Cited by 12 publications

(7 citation statements)

References 2 publications

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“…Netfleship, Henshaw, and Meyer (3), who first demonstrated that the substance induces pulmonary adenomas, noted also that it elicited many more of the tumors in A mice, the breed most prone to them spontaneously, than it did in C3H animals. Cowen (24) obtained data in RIII, CBA, and C57 mice which accord with this finding as do also the present results with adults of the C strain. Henshaw and Meyer (7) believed that the adenomas began to form within 1 to 2 months after the injection of urethane into 6 to 8-weeks-old animals of the A strain.…”

Section: Discussionsupporting

confidence: 92%

The Neoplastic Potentialities of Mouse Embryo Tissues

Smith

Rous

1948

Journal of Experimental Medicine

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In previous papers from this laboratory (1) experiments have been described which were made to learn how soon in the life of the organism cells possess the ability to become tumor cells. The neoplastic potentialities of various mouse embryo tissues, procured in the latter half of gestation, were tested by transplanting them to adults, together with methylcholanthrene. Tumors arose swiftly and in great diversity, yet it was questionable whether the cells exposed to the carcinogen were still in the embryonic state when they underwent neoplastic change, since the interval before the growths first became perceptible somewhat exceeded the time until birth, had the embryos been left undisturbed. If it had been possible to utilize the cells of very young embryos perhaps tumors could have been obtained within this period, but they did not survive the requisite exposure to methylcholanthrene, even when this was circumspectly injected into the "beads" along the uterus. Obviously for a decisive test of the neoplastic potentialities of embryo cells these must be exposed in utero to a carcinogen acting so speedily that its neoplastic effects will be evident almost at once. Recent authors who have produced pathological changes in mouse embryos with the Roentgen rays (2) have made no mention of tumor formation, and the polycylic hydrocarbons fail to pass the placenta in effective quantity. It was recalled however that the injection of the highly diffusible hypnotic, urethane, into adult mice of strains liable to pulmonary adenomas in old age causes these growths to appear earlier than usual and in much greater number (3). We had employed such a strain of animals when testing with methylcholanthrene the neoplastic potentialities of transplanted fragments of embryo lung, and had noted that multiple adenomas formed within 2 to 3 weeks (4). Consequently urethane was now injected repeatedly into pregnant females, and their offspring were searched for adenomas. These were sometimes visible in 3-day-old animals, and often had attained a considerable size within 10 days, none appearing in controls. The urethane could have acted in utero for only a few hours, and it produced no visible damage in the lungs of

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Section: Discussionsupporting

confidence: 92%

The Neoplastic Potentialities of Mouse Embryo Tissues

Smith

Rous

1948

Journal of Experimental Medicine

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“…When urethane is administered to mice at anaesthetic (1 mg/g body weight) or subanaesthetic doses, several carcinogenic changs have been observed (Henshaw & Meyer, 1944;Cowen, 1947;Klien, 1954;Boyland & Nery, 1965). Mice that spontaneously develop pulmonary adenomas will do so at a higher incidence than normal, and the tumours will occur earlier in life following a single injection of urethane (Cowen, 1947).…”

Section: Mutagenic and Anti-mitotic Evidencementioning

confidence: 99%

“…Mice that spontaneously develop pulmonary adenomas will do so at a higher incidence than normal, and the tumours will occur earlier in life following a single injection of urethane (Cowen, 1947). For example, greater than 75!1Jo of strain A mice normally develop pulmonary adenomas at 18 months of age.…”

Section: Mutagenic and Anti-mitotic Evidencementioning

confidence: 99%

“…This appears to be related to a decrease in resistance to infections resulting from bone marrow suppression (Cowen, 1947;Cruz & Mousstache, 1948;Moeschlin & Bodner, 1951). Urethane has been shown to cause a dose related bone marrow suppression in cats and dogs (Cruz & Mousstache, 1948;Moeschlin & Bodner, 1951).…”

Section: Genetics Of Lung Tumour Development In Micementioning

confidence: 99%

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Hazards of urethane (ethyl carbamate): a review of the literature

Field

Lang

1988

Lab Anim

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Urethane (ethyl carbamate) is used alone or in combination with other drugs to produce anaesthesia in laboratory animals. Although originally studied as a potential phytocide, urethane demonstrated antineoplastic properties when administered to rats with the Walker rat carcinoma 256. Subsequent trials in humans led to its use as a chemotherapeutic agent for various leukaemias. Mice develop pulmonary adenomas earlier in life and at a higher incidence following urethane administration. Urethane's carcinogenic influence is greater in neonatal mice; it also has a transplacental influence in mice. In rats, urethane increases the incidence of pulmonary adenomas, Zymbal Gland tumours, and a variety of other neoplasms. Urethane is absorbed sufficiently from the skin of laboratory animals to produce a transient narcosis. The carcinogenic effect appears to be due to an undefined oncogenic intermediate formed in the blood. Considering the properties urethane demonstrates in animals, the safety of its use by laboratory personnel is in question. However, if appropriate guidelines are followed, urethane should continue to be a useful anaesthetic agent for laboratory animals.

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“…Cowen (1947) and Selbie and Thackray (1948) Numerator: number mice with pulmonary tumours at stated age.…”

Section: Pulmonary Tumoursmentioning

confidence: 99%

Induction of Hepatomas in CBA/Cb/Se Mice by Hydrazine Sulphate and the Lack of Effect of Croton Oil on Tumour Induction in BALB/c/Cb/Se Mice

Biancifiori¹,

Bucciarelli²,

Clayson³

et al. 1964

Br J Cancer

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BIANCIFIORI, Bucciarelli, Santilli and Ribacchi (1963) described the occurrence of pulmonary adenomas and carcinomas in CBA/Cb/Se male and female mice treated with large doses of isoniazid or equimolar doses of hydrazine sulphate. The CBA strain was found by Orr (1947) to be the most resistant to the induction of pulmonary tumours of 6 strains tested with intranasal methylcholanthrene. However, tumour incidence was only slightly less in CBA/Cb/Se mice than in BALB/c/Cb/Se mice treated with large doses of isoniazid or hydrazine sulphate (Biancifiori and Ribacchi, 1962). In addition to the pulmonary tumours, hepatomas occurred in the same CBA mice and these are described here.When it had been shown that it was possible to induce pulmonary tumours in BALB/c and CBA mice with both isoniazid and hydrazine and liver tumours in CBA mice with hydrazine, it was thought interesting to attempt to promote skin tumours by croton oil following initiation with the one or the other compound. The BALB/c strain was chosen for this experiment. MATERIAL AND METHODSThe following solutions were prepared: 2 per cent aqueous isoniazid, 1 13 per cent aqueous hydrazine sulphate (i.e. equimolar with the isoniazid) and 1-30 per cent aqueous iso-nicotinic acid. Croton oil was 0 5 per cent in acetone. All the chemicals were pure and supplied by Farmitalia, Milan. Isoniazid, hydrazine sulphate and iso-nicotinic acid were given by stomach tube daily in a dose of 0-1 ml. per mouse and croton oil in a dose of 0 3 ml. which was painted twice weekly on the skin of the back after shaving with an electric clipper.Experiment I.-The mice were of the CBA/Cb/Se strain maintained in Perugia and the chemicals were given in aqueous solution by stomach tube daily for 36 weeks starting at 8 weeks of age as described by Biancifiori et al. (1963).Experiment II.-The mice were of the BALB/c/Cb/Se strain maintained in Perugia under the same conditions as in Experiment I.Treatment was started at 8 weeks of age and consisted of oral administration of isoniazid or hydrazine for 4 weeks, followed by croton oil for 30 weeks.

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Some Studies on the Action of Urethane on Mice

Cited by 12 publications

References 2 publications

The Neoplastic Potentialities of Mouse Embryo Tissues

The Neoplastic Potentialities of Mouse Embryo Tissues

Hazards of urethane (ethyl carbamate): a review of the literature

Induction of Hepatomas in CBA/Cb/Se Mice by Hydrazine Sulphate and the Lack of Effect of Croton Oil on Tumour Induction in BALB/c/Cb/Se Mice

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