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Abstracts Experimental Studies; Animal Tumors ABSTRACTS EXPERIMENTAL STUDIES; ANIMAL TUMORS Studies on the Artificial Production of Tumors by Chemical Substances, K. MuT~. Gann 29: 132-151, 1935. A review of the literature dealing with the artificial production of tumors. The author recognizes three periods. The first started with the failure of Hanau in 1889 to produce tumors in rats by tar and ended in 1915 with the epoch-making experiments of Yamagiwa and Ichikawa, who produced cancerous growths in rabbits’ ears after the repeated application of coal-tar. Beside this substance the following chemicals have been employed by numerous investigators in attempting to produce tumors in animals : xylolparaffin, scharlach R, sudan 111, indophenol, dimethylaminoazobenzol, amido- azobenzol, amido-azotoluol, a-naphthylamin, toluidin, glycerine, oleic acid, palmitic acid, indol, skatol, turpentine, and crude paraffin oil. The second period from 1915 to 1931 covers the experimental production of cancer in various animals by tar and tar products having unknown chemical formulae. During this period about 700 papers were written on this subject. The third period, from 1932 to the present, includes the brilliant work of Kennaway, Cook, and others on the fractionation of tar and subsequent preparation of a highly carcinogenic substance, 1 : 2 : 5 : 6 dibenzanthracene, Sasaki’s experimental production of hepatoma in animals by o-amido-azotoluol, and the very recent work of Kennaway and Cook on the conversion of deoxycholic acid of bile into a carcinogenic agent, methylcholanthrene. K. SUGIURA Further Studies on the Production of Dibenzanthracene Tumors in Pure Strain and Stock Mice, H. B. ANDERVONT. Public Health Reports 50: 1211-1217, 1935. The subcutaneous injection of mice with 1 : 2 : 5 : 6-dibenzanthracene in lard induced sarcomas that were transplantable to members of the strain of pure-bred mice in which the growths originated. Sarcomas could be elicited by a single injection of 0.8 mg. of dibenzanthracene, but repeated injections gave a higher percentage of tumors. A strain (CBA) that developed very few spontaneous mammary carcinomas was extremely susceptible to dibenzanthracene, though the tumors developed later than in strains with a high incidence of breast cancer. WM. H. WOGLOM Experimental Studies on the Transplantability of Hepatoma Produced by Means of Ortho-amidoazotoluol 1 : 3 : 4, T. IIKUBO. Experimentelle Studien uber die Transplantabilitat des mittelst o-Amidoazotoluols erzeugten Hepatoms, Gann 29: 79-87, 1935. The author reports successful subcutaneous transplantation of hepatoma produced in rats some seven to ten months after feeding with o-amidoazotoluol and p-amidoazobenzol, or by feeding o-amidoazotoluol alone. One of the two subcutaneous transplants was carried successfully for five generations. The subcutaneous transplantations gave positive results in 35 out of 66 inoculated animals. The transplantability seemed to increase from generation to generation, so that at the fifth generation 12 out of 14 rats gave positive growths. On the other hand, in the first generation, a growth was found in only one out of 6 rats. The histologic picture of the subcutaneous and intraperitoneal tumors was identical with that of the original. The article is illustrated by photographs and photomicro- graphs. K. SUUIURA [These interesting results give definite evidence of the malignant nature of the liver tumor artificially produced by an organic compound, but also show that the phenanthreric 659 660 ABSTRACTS nucleus is not an essential part of a carcinogenic substance, though the work of Kenn- away, Cook, and their collaborators has proved that a large number of compounds containing this group are highly effective producers of cancer. Similarly, Morton and Clapp (Science 82: 134, 1935. Abst. in Am. J. Cancer 25: 415, 1935) have shown that symmetrical triphenylbenzene and tetraphenylmethane are feebly carcinogenic. Yo- shida’s original paper on the production of hepatoma by o-amidoazotoluol was printed in the Proceedings of the Imperial Academy of Japan 8: 464, 1932. For abstracts of other papers by Yoshida see Am. J. Cancer 19: 97, 1933; 22: 137, 1934; 24: 676, 1935. The original article gives details as to the feeding. One gram of o-amidoazotoluol is dissolved in 20 C.C. of warm olive oil and, after cooling, a volume of olive oil is added to make 20 gm. This solution is then thoroughly mixed with rice so that 1 gm. of rice contains 1 mg. of o-amidoazotoluol. An animal will consume daily about 5 to 10 gm. At the same time some fresh green food is given. Since the azotoluol is toxic to many of the rats, the experiment must be conducted with a large number of animals. After about two months of this feeding the liver cells show fatty atrophy in the center of the lobules with proliferation at the periphery. After five to eight months marked adenoma- tous proliferation is seen, and in those animals which survive after nine months a typical carcinoma of the liver develops. The statement by Fischer-Wasels that he has been unable to repeat Yoshida’s work is nullified by the fact that he does not mention the substance he used (Verhandl. d. deutsch. path. Gesellsch. 28: 66, 1935).-E~.] Production of Tumors by Organs from Tumor Animals, FERDINANDBLUMENTHAL. Ueber die blastomatosen Eigenschaften von Organen von Tumortieren, Bull. schweiz. Vereinig. f. Krebsbekampf. 1 : 62-66, 1933. The author reviews the experiments of the past few years on the transfer of propagable new growths by means of blood or other organs from their bearers, and decides that the successful outcome is not due to the presence of metastatic tumor cells. One of the principal reasons for his belief is the statement that even embryos from a tumor-bearing mother will transmit the neoplasm, for the passage of tumor cells through the placental barrier is hardly conceivable. All this suggests the presence of a diffusible etiological agent of some sort, and if the findings may be applied to man, it would appear that malignant disease is not entirely eradicated by excision of the neoplasm. The agent still remains at large, and all possible measures (radiation, diet, endocrine treatment) must be directed against it even though the growth itself may seem to have been successfully removed. [There is no intimation in this paper that some investigators have failed to transmit tumors by ihjecting the organs of their bearers.] WM. H. WOQLOM Cellular Allergy and Carcinogenesis, 0. REUTERWALL.tfber cellulare Allergie und Krebsgenese, Ztschr. f. Krebsforsch. 42: 117-139, 1935. With allergy as a basis, a working hypothesis can be constructed that neglects neither carcinogenic agent nor predisposition. Two experimental methods are available for inquiry into the significance of allergic irritation for neoplasia. The carcinogenic activity of recognized allergic agents can be tested, and the allergic properties of known carcino- genic substances investigated. Both have been employed in the experiments which this paper describes. In respect to the former, repeated injection of serum or egg albumen into the rabbit’s ear was found to induce proliferative changes but nothing resembling malignant growth. As for the latter, the lesions following the injection of tar or 1 : 2 : 5 : 6- dibenzanthracene are discussed, and emphasis is laid on the long period that elapses between introduction of the carcinogenic agent and the appearance of the malignant transformation. The allergic irritation and its immediate consequences would thus seem to be but the first link in a long chain of events. The nature of the subsequent links cannot yet be explained; there are many possibilities-physical or chemical alterations in the cell, irreparable damage to its division mechanism, somatic mutation, perhaps a virus that becomes operative when the resistance of the cell has been broken down, or, most promising of all for investigation, surface changes. EXPERIMENTAL STUDIES ; ANIMAL TUMORS 661 Seven photomicrographs and two photographs of gross specimens illustrate this paper. WM. H. WOQLOM Origin of the Inflammatory Epithelial Proliferation in the Experiments of B. Fischer, M. A. ZACHARJEWSKAJA. Uber die Genese der entzundlichen Epithelwucherungen im Versuch von B. Fischer, Ztschr. f. Krebsforsch. 42: 209-221, 1935. The injection of scharlach R and other substances into the rabbit’s ear, as practised by B. Fischer-Wasels and others, gives rise to an epithelial hyperplasia that is morpho- logically suggestive of carcinoma. Two explanations for this reaction have sprung up. One, espoused by Fischer-Wasels himself, ascribes it directly to specific chemical stimula- tion by the exogenous agent. Other investigators, however, while accepting this hypothesis in a general way, believe that mechanical or circulatory factors are required in addition. The second explanation suggests that the epithelial hyperplasia is but secondary to inflammatory or circulatory changes in the underlying connective tissue, the exogenous factor thus having significance only in so far as it excites these lesions. As a result of his own experiments the author comes to the following conclusions: Two types of epithelial proliferation follow the injection of scharlach R into the rabbit’s ear. In the first, growth begins in the hair follicles, and the epithelium retains its differentiation. In the second type, which has its inception in the first, differentiation is lost. Both varieties reach their acme where there are advanced inflammatory changes in the connective tissue, and the second type, indeed,
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