O N T H E ACTION OF X-RAYS UPON THE TRANS- PLANTATION OF A SPONTANEOUS CARCINOMA OF THE RAT.l

By HELEN CHAMBEES, C.B.E., M.D., GLADWYS SCOTT, and S. Russ, D.Sc.

From the Cancer Resenreh Laboratories, llliddlesex Hospital.

(PLATE XIX.)

IN December 1 9 1 8 , one of the rats in the ariinial house of these laboratories was found to have a spontaneous tumour in the neck. A n operation was kindly carried out on the aniinal by Dr. J. A. Murray, of the Iniperial Cancer Research Fund, and an encapsuled tumour of the submaxillary gland removed. Autologous inoculations were made and transplantation attempted into twenty-two normal rats, the latter without success. The tuiiiour did not recur a t the primary site after removal, but very large tumours developed as a result of the autologous grafting.

I n view of the comparative rarity of spontaneous carcinoma of the rat (seventeen cases have been recorded), and the difficulty that generally attends the propagation of sporitaneous tumours in normal animals, we were led to see whether the transplantation could be facilitated by exposing the animals to X-rays before inoculation. The basis for this procedure was founded 011 work with Jensen’s rat sarcoma, and was as follows:

It has been shown (1917 ’) that when rats which are immune to iiioculations of sarcoiiia are given a very large dose of X-rays, their immunity is temporarily broker1 clown, and a subsequent inoculation results in some growth of tumour. Moreover (1 9 1 9 z, when normal rats are given very siiiall doses of X-rays daily, they become less szis- ceptible to subsequent inoculations of sarcoma. By suitable choice, then, of the X-ray dose, i t is possible to encourage or discourage the growth of tnmour and this without any irradiation of the cells of the tumour itself. The dose of X-rays which makes a rat more suscept- ible to the growth of inoculated sarcoma has been found by exposing batches of rats to different doses of X-rays, then inoculating them and recording the size of the tunionrs which develop.

The data in Table I. show the effects of irradiation for ten minutes Received March 31, 1920.

CARCINOMA OF THE RAT. 3 85

10

and for one minute before inoculation. In both cases the resulting tuniour growth was greater in the X-rayed than in the control animals.

days before inocu1:rtion

One minute X-rays tcn

TABLE I.

Number of Rats. Conditions of Radiation. Size of Tuinour compared with Control Toiiiours Twenty-fire

da! s after Inoculation.

1’60

1‘38

Guided by these results, it was decided to see whether the smie treatment would help in the propagation of the spontaueous carcinoma. Seven rats were given a rather large dose of X-rays, fifteen niin- utes’ exposure to unscreened X-rays, under conditions specified in the paper already cited (1 9 19 ”. This exposure is nearly equivalent to one-half of the unit which we have adopted in this work, naniely, the Rad-this unit being the amount of X-ray energy required to produce a lethal effect upon malignant cells.

The day after the X-ray exposure, the seven rats were inoculated with small pieces of carcinoma. The first of such attenipts, v ide Fig. 1, column C, resulted in the growth of a tumour in one animal.

Subsequent inoculations in X-rayed animals yielded a larger percentage of successful inoculations, vide columns D and E. At this stage i t was decided to attempt once more transplantation into normal animals, inoculation in to X-rayed animals being niade simultaneously.

Columns F and G bring out in rather striking contrast the difference in behaviour of normal and heavily X-rayed rats. Subse- quently it was found possible to propagate the tumour in nornial rats. vide HI.

The General Behaviour and Histological Stmetwe of the Carcinoma.

The microscopic structure of the growth has been maintained fairly constantly throughout the transplantations. I t closely resembles spheroidal-celled carcinoma of the breast as it occurs in man.

Plate XIX. Fig. 1, shows the marked alveolar arrangement, the cells form solid masses with no tendency to form acini, and in this respect this carcinoma differs from the E’lexner-Jobling rat carcinoma. The amount of connective-tissue stroiiia varies in different parts of the growth, being considerable in amount in some places, and in others so scant that the growth has a structure almost sarcomatous in character. Cystic degeneration of the tumour has often occurred, large necrotic

386 HELEN CHAMBERS.

areas form, with subsequent fluid transformation of the contents (Plate XIX. Fig. 2 ) .

The rate of growth was a t first extremely s low; with frequent transplantation i t has become much faster, a phenomenon frequently described after successful transplantation of spontaneous tumours.

JOURNAL OF PATHOLOGY.-YoL. X X I I I .

V l C . 2.

PLATE SIX.

FIG. 3.

CARCINOMA OF THE RAT. 387

Metastases have occurred in three of the rats in the niediastinal The secondary ~lodules had glands and lungs (Plate XIX. Fig. 3).

the same histological structure as the original tuinour.

CONCLUSIONS.

Apart from the significance of these observations to other laboratory workers who wish to propagate spontaneous turnours-and in this connection we may refer to the attempts of Xlann (1919 3, to propagate a mammary carcinoma of the dog in 134 animals without suc- cess-it seems to us that they have a direct bearing on the treatment of malignant disease by radiation. The inoculation of an auinml with a small piece of transplantable tuniour resembles the formation of a metastasis rather than that of a spontaneous tuniour, so that our observations direct attention rather to the question of the appearance of metastases, or to the recurrence of a growth after operation, than to the occurrence of a primary tnmour.

The experiments indicate a lowering of the animal’s resistance to the growth of malignant cells, if i t be given a rather large generalised dose of X-rays; a result exactly the reverse to what occurs if the animal be given a series of exposures to very small quantities of X-rays. This transition from a state of increased resistance to one of lowered resistance has been worked out in some detail for Jensen’s ra t sarcoma ; the data will be found in a paper, “ Experimental Studies with Small Doses of X-rays,” now in the course of publication.

W e have great pleasure in recording our thanks to Dr. J. A. Murray, of the Iniperial Cancer Research Fund, for his help and advice in the early stages of the transplantation of the tuniour.

R1I:FELtENCES.

1. MOTTRAM AND Russ . . . P ~ o c . Roy. Soc. London (X), 1917, vol. xc. 11. 1. 2. RUSS, CHbMBERS, SCOTT, Lancet, London, 1919, VOl. i. 11. 692.

AXD MOTT~~AM 3. MANN . . . . . . . .Joicm. Cmcer Reseaxh, October 1919, vol. iv.

No. 4, p. 331.

DESCRIPTION O F PLATE SIX. FIG. l.-Drawing of Iuicroscopic c1i;irscters of tmiour.

FIG. 2.--Nsked-eye aplicaraiice of cystic tlegeiieration.

Fic. 3.-hkt;istnses i n Iniigs md. nrediastiiinni.

( x 130).

( x 130). ( x 130).

26 -JL. OF PATH.-VOL. XXIII.