THE GASEOUS METABOLISM IN RATS INOCULATED WITH MALIGNANT NEW GROWTHS.

By W. CRAMER, Ph.D., D.Sc.

LECTURER ON PHYSIOLOGICAL CHEMISTRY AND ASSISTANT TO THE PROFESSOR OF PHYSIOLOGY, UNIVERSITY OF EDINBURGH.

THIS investigation is the first attempt to study the influence of the growth of a neoplasm on the metabolism of an otherwise normal animal. The experiments were carried out on young white rats into which a quickly growing tumour had been transplanted. The parent tumour was a tumour of the 13th generation of the strain J. R. S.* The transplantations were made into the right axilla on June 10th, 1908, into three young rats belonging to a litter (Litter B) of six rats, born May 1st, 1908. The remaining three rats were kept as controls. Small doses (0.05 c.c.) were used for transplantation. Seven days after the inoculation the tumours could be felt. They then grew rapidly, and soon extended over the whole right side. Notwithstanding the enormous size of the tumours, the weight of which, a month after the inoculation. when the animals were killed, amounted to almost a third of the weight of the host, the animals appeared to be quite healthy. The coat looked smooth; the animals were very active and appeared to be well nourished. The animals were killed on July 8th, before any signs of emaciation appeared. At the necropsy fat was found in the peritoneal cavity of the tumour-animals although not nearly as much as in the control-animals. A most unexpected result was obtained by comparing the weights of the tumour-animals with the control-animals.

Table I. shows that on June 19th, when the tumours were still quite small, the tumour batch weighed 30 gr. more than the control-animals. On July 1st the three normal rats weighed 50 gr., 50 gr., and 70 gr. respectively, while the tumour rats had a weight of 80 gr., 80 gr., and 90 gr. The differences in weight cannot of course be accounted for solely

* A transplantable spindle-celled sarcoma of the rat for which the Imperial Cancer Research Fund is indebted to Professor C. O. Jensen of Copenhagen.

by the weight of the tumours, since these hardly reached such a weight a week later, as will be be seen from the following figures:

It will be seen that the growth of the tumours appears to have had a distinctly favourable influence on the growth of the animals in the earlier stages. In the later stages, however, after the tumour had reached a weight or that of the animal which served as a host, the growth of the animals had been retarded.

The method used for the estimation of the gaseous metabolism was the one devised by Haldane and Pembrey. All the precautions recommended by these authors (weighing against dummy tubes and a dummy animal chamber, insertion of control tubes, etc.) were observed. In order to exclude individual variations as much as possible, the gaseous metabolism of the three tumour rats together, and of the three normal rats together, was determined. The temperature of the room in which the estimations were made was fairly constant, and as a rule the tumour batch and the control batch were subjected to the experiment on the same day.

Table I. gives the results of the estimations of the gaseous metabolism of the fasting animals, i. e. 18-24 hours after feeding. In every case the experiment lasted 60 minutes, so that the figures given for the CO2 and H2O discharged represent the actual amounts found in one hour.

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The results show that no essential difference exists between the metabolism of the tumour-rats and the control-rats. The respiratory quotients are the same in both batches, and vary within the limits observed by Pembrey and Spriggs for fasting rats. Taking the individual animal as the unit, the amount of CO, discharged and O, absorbed is higher in tumour rats than in the normal rats. The more energetic metabolism of the tumour rats is accounted for by the more rapid growth of the organism which served as a host. The growth of the tumour itself

does not appear to have a marked influence on the gaseous metabolism of the fasting animals.

An interesting difference was observed in the metabolism of the animals after a meal of bread and milk. Preliminary observations confirmed those of Pembrey and Spriggs, that the rise of the respiratory quotient after a meal rich in carbohydrates was due to an increase in the CO, excretion, the absorption of O, remaining almost the same as in the fasting condition, as the following figures show :—

In order to study more minutely the changes in the CO, excretion taking place after a meal, a series of half-hourly estimations of the CO2 excretion only, were made after the animals had been fed on bread and milk. The results are given in Table II. The experiments were made July 7th.

The results show that the rise in the CO, excretion is much more pronounced in the normal rats than in the tumour rats, so much so, that in the third hour after the meal the normal animals excrete more CO2 than tumour rats, although in the fasting condition the reverse condition. obtains. Since the O, absorption is not materially affected by the feading of the animals, the respiratory quotient can be roughly calculated on the basis of our former estimations of the O2 absorption. It is then found that it rises considerably above unity in the normal animal, and remains above unity for several hours after feeding, while in the tumour animals it hardly exceeds unity and rapidly falls again. It may be noted that the respiratory exchange of the tumour-rats returns sooner to the fasting condition than that of the normal animals.

*Pembrey and Spriggs, Journal of Physiology, vol. 31, 1904, p. 320.
†These estimations were made in the 3rd and 4th hour after feeding.

3 Normal rats. [Weight 190 g. Fed with 20 g. bread

The rise in the CO2 excretion has been interpreted by Hanriot, and by Pembrey and Spriggs as being the result of chemical processes, which lead to the transformation of carbohydrates into fats, CO, being split off. If this interpretation is accepted, it can be concluded from our observations that in the tumour-rats such a storing of the absorbed food-material in the form of fat does not take place at all, or not to the same extent as in normal animals.

It is not difficult to understand why this should be the case. The rapid growth of the tumour-cells is the result of their absorbing more nutritive material than the cells of the organism in which they grow. In the normal animal the mechanism which presides over the assimi