E X P E R I M E N T A L CARCINOGENESIS 481

REFERENCE

BURNET, F. M. . . . . . . 1940. Awtral. J . Exp. Biol. Med. Sci., xviii, 353.

616-006 . 384-021 . 6 (Cuniculus) : 547 . 689 (cholanthrene) AN UNSUCCESSFUL ATTEMPT TO INDUCE GLIOMATA I N

RABBITS WITH CHOLANTHRENE

HELEN RUSSELL

From the Departments of Pathology in the University of Edinburgh, and the Christie Hospital, Mancheater

(PLATE LXX)

This experiment was the sequel to a study of human gliomata (Russell, 1941) and its object was to find out what types of tumour growth might develop in the brain of the rabbit in response to the presence of a carcinogen.

The polymorphism of human gliomata is well known and has led to the remarkable histological subdivisions inaugurated by Bailey and Cushing ( 1926).

Experimental attempts to induce gliomata in the mouse brain by the implantation of carcinogens have resulted in twnours which have been con- sidered analogous to the human types and with as wide a range of variation in morphology. Various carcinogens were employed ; methyl cholanthrene by Seligman and Shear (1939) and Zimmerman and Arnold (1941), and 1 : 2 : 5 : 6- dibenzanthracene contained in cholesterol pellets by Peers (1940). Experiments with rats and rabbits have been less numerous and less successful (Bertrand and Gruner, 1938, using 1 : 2-benzpyrene ; and Oberling et al., 1936, using 3 : 4-benzpyrene).

It was hoped that the rabbit brain, being larger than that of the mouse, might provide a more suitable medium in which to study neoplasia ; further, it is very easy to implant material into the cerebral cortex of the rabbit without fear of inducing more than a minimal mesodermal reaction from the meninges and tissues of the scalp. On the other hand it was realised that rabbits do not seem to respond to carcinogens so readily as mice, and that, as their span of life is greater, a longer experiment would be necessary.

The rabbits were divided into experimental and control groups ; the former being implanted with cholanthrene-a known carcinogen, the latter with anthracene, which has no carcinogenic activity. These substances were used in pure form compressed into pellets of about 20 mg. weight. By this means chemical injury to the brain from organic solvents and the complication of phagocytic reaction around fat solvents were avoided. Three sites were chosen for the implants- the cerebral cortex, the eye and the cerebellum. The cerebral cortex implant is by far the easiest operation and the results in that group are those to which most attention was paid. In the cerebellar operation bleeding may be so profuse that the pellet becomes displaced, and in the eye operation the 20-mg. pellet was too large for a safe trephine hole and smaller doses had to be used.

The animals were bought in the open market in 1941 and varied in age, weight and breed. Most of them were infected with coccidiosis and a few had helminthic infections ; their blood counts were as variable as was to be expected in such a mixed group. .At intervals during the four and a half years of

The experimental details are summarised in the accompanying table.

482 H. RUSSELL

the experiment some of the animals died of intercurrent disease but about half the original number were fat and well at the end of 1945 when the experi- ment was ended. The results were negative ; no indication of tumour growth was found in any of the rabbits at any time.

TABLE

Detaik of an unsuccessful attempt to induce g l i o m t u in rabbits

Pellet of cholanthrene Rabbit no. Site of implant I o~ anthracene (wt. in mg,) Survival after implant

EXPERIMENTAL GROUP (CHOLANTHRENE)

218 220 222 224 226 228 230 232 * 234 236 238 240 242 244 246 262 264 266 268 270

Cerebrum

E;.e

Cerebellum

20 20 20 15 15 15 15 20 20 20 20

c. 4 c. 4 c. 4 c. 4

20 20

c. 12 c. 15 c. 12

CONTROL GROUP (ANTHRACENE)

4 yrs. Died 43 11 Killed 4 months Died 43 yrs. Killed 44 , 9 Died 43 1 9 Killed 44 ,, Died 43 ,, Killed

153 months Died 43 yrs. Killed 93months Died 44 yrs. Killed 5 months Died 4) yrs. Killed 33 ,. Died 43 ,, Killed 4,; I , Died 43 , 9 Killed 4) 11 Killed 3& ,, Died

213 215 217 219 221 241 243 263 265

I

Cerebrum ,?

E;e

Cerebellum

20 20 20 10 20

c. 4 c. 5

c. 12 c. 12

20 months Died 4 yrs. Died 43 ,, Killed 44 11 Died 2 A 1 9 Killed 43 9 , Killed 43 ,, Killed 44 ,, Died 43 9 , Killed

* See figs. 1 and 2.

There is little to be said about the histological reaction of the nervous tissue to the presence of either anthracene or cholanthrene in this form. The pellets were implanted aseptically and remained in the brain as immobile foreign bodies, generating around them minimal glial reaction (figs. 1 and 2 ) in which mesodermal giant cells were sometimes recognised.

These negative observations are published in order to emphasise the importance of factors other than the carcinogen in neoplasia, factors which are not only species specific but which may even have a limited distribution within a given species.

J. PATH. BACT.-VOL. LIS

EXPERIMENTAL CARCINOGEXESIS

PLATE LXX

FIG. 1.-Section of brain in rabbit 232 showing tho pocltct of rcxtion formed in the cerebral cortex around il cholanthrcne pellet which had bccn implanted 43 years before. x5.

FIG. 2.-Higher power view of part of the wall of the pocket which contained the cholanthrene pellet, showing minimal glial reaction. x 50.

C A R C I N O M A COLI I N U L C E R A T I V E C O L I T I S 483

Summary

This paper is the record of an unsuccessful attempt to induce gliomata in rabbits by implanting a pellet of cholanthrene into parts of the nervous system. No tumours developed, although about half of the animals survived for four and a half years after the implantation had been carried out.

I have to thank Professor Murray Drennan for allowing me to undertake this long experiment in his department, Dr William Blackwood for examining specimens from animals which died while I was away from Edinburgh, and Dr A. Haddow for the cholanthrene and anthracene pellets.

REFERENCES

BAILEY, P., AND CUSHING, H. . BERTRAND, I., AND GRUNER, J. . OBERLING, C., GU~RIN, M., AND

PEERS, J. H. . . . . . . RUSSELL, H. . . . . . . SELIGMAN, A. M., AND SHEAR,

ZIMMERMAN, H. M., AND ARNOLD,

GU~RIN, P.

M. J.

HILDEGARDE

1926. A classification of the tumors of the

1938. Bull. de 1’Assoc. p . l’dtude du

1936. Compt. rend. SOC. de biol., cxxiii,

1940. 1941. 1939.

glioma group, Philadelphia.

Cancer, xxvii, 697.

1152. A m r . J . Path., xvi, 799. Edin. Med. J., xlviii, 145. A m r . J . Cancer, xxxvii, 364.

1941. Cancer Research, i, 919.

616 . 348-002-006 . 4 6 EXTENSIVE CARCINOMATOUS CHANGE I N A CASE OF

CHRONIC ULCERATIVE COLITIS

W. McI. ROSE From the Department of Pathology and Bacteriology,

University of Lee&

The incidence of malignant change in cases of chronic ulcerative colitis has been the subject of many communications in the literature of the United States, but no paper has been found in a search of English journals covering the past twenty-five years. This case is reported briefly, for it presents most of the features said to be characteristic of the condition, and so may lead to a better recognition of this interesting association.

Case report

Mrs G. P., aged 27 years, was admitted to the General Infirmary at Leeds on 20.8.46 complaining of recurrent lower abdominal pain and diarrhea. She stated that she had first suffered from an attack of diarrhea in 1938 when, a t the age of 18 years, she was confined to bed under medical care for six weeks. Since that time she has been subject to recurring attacks lasting about a month, followed by remissions of variable length, the last and longest of which was of about one year’s duration. The attacks consisted in passing about ten watery stools in 24 hours ; only on rare occasions had she noticed any mucus or blood. Her appetite remained good in these relapses, and she was not much inconvenienced, for over the years she had been married and had borne a eon who is now four years of age and healthy.

Clinical history.