Influence of Carbamic Esters (Urethanes) on Experimental Animal Tumours

Haddow, Alexander; Sexton, W. A.

doi:10.1038/157500a0

Cited by 168 publications

(40 citation statements)

References 20 publications

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“…Various possibilities exist; one is that urethane, resembling so many normal tissue components, substitutes for one or more of them and upsets metabolism. Haddow and Sexton (1946), in their work on the inhibition of the Walker rat tumnour by urethane, suggest an upset of purine metabolism. This would fit in with the present results, since pentose nucleotides, here shown to antagonize the action of urethane, contains purine and pyrimidine compounds.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of the Carcinogenic Properties of Urethane by Pentose Nucleotides

Pn¹

1949

Br J Cancer

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URETHANE, which induces lung tumours in mice and rats (Nettleship and Henshaw, 1943; Jaffe, 1947; Cowen, 1947), also causes a notable decrease of malignant and normal leucocytes (Paterson, Haddow, ApThomas and Watkinson, 1946; Cowen, 1947). The present study was undertaken to investigate any correlation between the carcinogenic and leucopaenic properties of urethane.The mixture of pentose nucleotides as prepared from yeast nucleic acids is used clinically in the treatment of agranulocytosis, and it has been found to elicit leucocytosis in mice (Parsons, 1945). Since pentose nucleotides have the opposite effect of urethane with respect to their action on leucocytes, the possibility that the carcinogenic effect of urethane might be antagonized by pentose nucleotides was considered. MATERIALS AND METHODS.The mixture of pentose nucleotides used was the commercial preparation, as supplied by Menley & James Ltd. in 10 c.c. sterile vials, each containing 0-7 g. of a mixture of the sodium salts of the four nucleotides of yeast ribonucleic acid preserved with 0-3 per cent cresol.The mice used were the F1 cross of the A and C 57 lines. These were chosen because A mice have a relatively high spontaneous lung tumour incidence (Bittner, 1939;Heston, 1940), and it has been observed that such strains respond more readily to the carcinogenic effect of urethane (Cowen, 1947). The hybrids would also tend to have a high spontaneous incidence, since the inheritance of spontaneous lung tumours in this cross seems to be due to a single dominant gene (Bittner and Little, 1937;Bittner, 1938).Seventeen A x C 57 males approximately two months old were injected with the pentose nucleotides solution subcutaneously at the flanks, daily at midmorning. The dosage was 0-1 c.c. for 3 days, 0-2 c.c. for 4 days, 0-4 c.c. for 1 day, and then a 0-1 per cent solution of urethane was substituted for the drinking water. After continuing to inject 0-4 c.c. of pentose nucleotides for a week the mice started to show ill effects. Both treatments were discontinued (after 2 weeks of pentose nucleotides and 1 week of urethane treatment) for two days, to rest the mice. On resuming treatments the dosage of pentose nucleotides was decreased to 0-3 c.c. daily. This rate of dosage was tolerated much better.Eight weeks from the time of the first injection the urethane solution was replaced by tap water, and four days later the injections of the pentose nucleotides were stopped.

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Section: Resultsmentioning

confidence: 99%

Inhibition of the Carcinogenic Properties of Urethane by Pentose Nucleotides

Pn¹

1949

Br J Cancer

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“…Todd (quoted by Haddow and Sexton, 1946) suggested that urethane may interfere with nucleotide synthesis. In support of this Cowen (1949) demonstrated that the induction of lung tumours by urethane was inhibited by the simultaneous administration of pentose nucleotides.…”

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confidence: 99%

“…Later (Boyland and Koller, 1954), it was found that simultaneous administration of thymine reduced the incidence of abnormal mitosis due to urethane in the Walker rat carcinoma 256. Haddow and Sexton (1946) suggested that urethane may interfere with purine synthesis. There is evidence (Roe, 1955) that simultaneous administration of the purine precursors, glycine and formate, inhibits the initiation of skin tumour-formation by urethane (Salaman and Roe, 1953).…”

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Pulmonary Tumours in Urethane-Treated Mice: Failure to Demonstrate an Underlying Infective Aetiology

Firth¹,

Roe²

1955

Br J Cancer

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“…Urethane inhibits tumour growth in experimental animals (Haddow and Sexton, 1946) causes a decrease of normal and malignant leucocytes (Paterson, Haddow, Ap Thomas and Watkinson, 1946), and inhibits mitosis (Lasnitzski, 1949;Hughes, 1950). In the (lithiocarbamate series sulphur replaces the oxygen of the carbamic acid radicle.…”

mentioning

confidence: 99%

Effect of Dithiocarbamates on Sarcoma Cells and Fibrocytes Cultured In Vitro

Ak¹

1954

Br J Cancer

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Influence of Carbamic Esters (Urethanes) on Experimental Animal Tumours

Cited by 168 publications

References 20 publications

Inhibition of the Carcinogenic Properties of Urethane by Pentose Nucleotides

Inhibition of the Carcinogenic Properties of Urethane by Pentose Nucleotides

Pulmonary Tumours in Urethane-Treated Mice: Failure to Demonstrate an Underlying Infective Aetiology

Effect of Dithiocarbamates on Sarcoma Cells and Fibrocytes Cultured In Vitro

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