ONE of the most recent and important additions made to the list of carcinogenic compounds was the discovery by Nettleship, Henshaw and Meyer (1943) that pulmonary tumours (but no other types of cancer) were induced in C3H and A line mice by intraperitoneal injections of urethane. Subanaesthetic doses of 1 c.c. of a 10 per cent solution per 100 g. body weight of mouse were effective in producing tumours in A mice in less than 4-months (Henshaw and Meyer, 1944).It was also effective when given by crystal implantation or in the drinking water (Henshaw and Meyer, 1945). Other hypnotics and many substances more or less related in their chemical structure to urethane were ineffective (Larsen, Rhoads and Weed, 1946). Jaffe (1947) found that urethane would produce both lung and liver tumours-in rats.The chemical simplicity of this potent carcinogen compared with others makes it rather remarkable, especially since it is by no means unrelated to many compounds which are normally present in living organisms. The following work was undertaken in order to obtain more information about the methods of action of urethane and the reason for its specificity for lung. MATERIAL AND METHODS.Groups of about ten animals of each sex of three inbred lines of mice (CBA. R III and C57), aged about two months, were injected intraperitoneally with 0-25 c.c. of 10 per cent aqueous urethane solution weekly for 14 weeks, as was done by Nettleship, Henshaw and Meyer (1943). This was a fully hypnotic dose. At first the animals were kept five in a cage, virgin and non-breeding. All animals surviving the treatment were killed off either at seven months after the beginning of the treatmient for further experimental studies, or at ten months for examination.At the same timne and under identical conditions, 21 male and 20 female CBA mice, also aged about two months, were injected weekly with 0-2 c.c. of a freshly made 12 per cent solution of veronal (sodium diethylbarbiturate) intraperitoneally for 14 weeks. This was also a hypnotic dose. Seven males and five females of those that survived treatment were killed at seven months and the rest at ten months after beginning the treatment. RESULTS.It was known that the incidence of spontaneous lung adenomas varied in the three lines of mice used, though precise figures are not available. However, it can be stated, in general terms, that the RIII line shows about 10 per cent lung tumours after one year, the CBAs rather rarely have anv at this age, and none have been found in the C57 line at any age.

IN a previous paper (Cowen, 1947) (Bittner, 1938).Although urethane has been mentioned as carcinogenic for mouse (Nettleship and Henshaw, 1943) and rat lung (Jaff6, 1947) this action has not yet been reported in other animals. Chickens and guinea-pigs were therefore given prolonged treatment with urethane in order to determine if they were susceptible to its carcinogenic action. MATERIAL AND METHODSIn order to study the inheritance of the strain difference, A and C57 raice were crossed to give their Fl and backerosses. Since the inherited susceptibihty to most known cancers is due to dominant genes this was anticipated here, and consequently a large number of the C57 backcross mice were bred in order to note segregation, which should be manifest in the group on this assumption.The urethane was adrninistered by dissolving it in the drinking water of the m,ice. This proved to be effective in ehciting tumours by Henshaw and Meyer (1945) and Cowen (1949). Preliminary experiments indicated that the various strains and crosses of mice used did not differ in their fluid intake, and consequently strain differences due to this treatment were not due to a different intake of the carcinogen.All the mice were approximately 2 months old at the start of the experiment. Their food consisted only of the 14 per cent rat cake, nuts as supphed by the North-Eastern Agricultural Co-operative Society, Aberdeen. %he mice were given a 0-1 per cent solution of urethane in tap-water in place oftheir d ;V"v water. No other water was available since the food of the mice was dry. After 3 months of this urethane treatment the solution was replaced by tap-water for 4 months, after which time the mice were sacrificed. The urethane given to all the mice came from the same stock solution, which was made up in 10 litre quantities at a time.

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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