Gastric cancers removed from 100 patients were divided into seven types according to the activity of the following four kinds of enzymes, aminopeptidase, β-esterase, succinic dehydrogenase, and glucose-6-phosphate dehydrogenase, whose presence has been testified in the specific types of cells in the normal and metaplastic gastric mucous membrane. Based on the histochemical finding, a new classification of gastric carcinoma is proposed, and this classification reveals a close correlation between the enzymic pattern and the mode of spreading of the cancer. Prognostic significance of the new classification of gastric carcinomas is emphasized.

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Antibody highly specific to human β_1c-globulin has been produced in rabbits by incomplete Freund's adjuvant containing human complement (C') adsorbed onto zymosan. However, in reference to its complement activity as the third component of complement (C'3), hemolysis of EAC'142 cells was noticed only on the cathode side of the region corresponding to the electrophoretic pattern of β_1c, using immunolyso-electrophoresis.
Consequently, the immunospecificity of the fluorescein-conjugated anti-β_1c-globulin method for detection of cell-bound antibody was checked in a model system consisting of an isografted ascitic form of mammary tumor in a C3H/He mouse (MM₂) and of syngeneic anti-MM₂ antiserum.
The conclusion was reached that anti-human β_1c-globulin conjugated with fluorescein could be used as an immunospecific stain for the histochemical detection of the MM₂-antibody-C'1423 complex.

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Methylcholanthrene-induced mouse sarcoma cells in tissue culture were destroyed by lymphoid cells from syngeneic mice which had been immunized against the same tumor. The effect was demonstrated by production of macroscopic foci of tumor cell destruction in monolayer cultures, and by release of ⁵¹Cr from labeled tumor cells, and was also observed by time-lapse cinemicrography. Serum or peritoneal fluid from the same mice had no effect. Complement was not required for the reaction.
Target tumor cell monolayers growing on Millipore membrane were destroyed when lymphoid cells from immune donors were grown on the other side of the membrane. These results suggest that the immune lymphoid cells elaborate some diffusible substance or substances which play an important role in "cell-mediated" tumor specific reactions.

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Tumor cell mitochondria having high ratios of P:O (ADP/O) and respiratory control were obtained from several ascites tumor cells by a mild osmotic shock in the step of cell disruption, and their respiratory capacity and electrophoretic mobility were examined to clarify their difference from normal tissue cell mitochondria.
The respiratory activities of tumor cell mitochondria were unstable in a medium without albumin compared with those of mouse liver mitochondria, and the electrophoretic mobilities of intact mitochondria, regardless of source materials, were much smaller than those of damaged mitochondria. Furthermore, the increase of mitochondrial mobility was demonstrated to parallel the decrease of respiratory control ratio caused by storage in an oxygen-deficient medium or by repeated washings, indicating the loss of mitochondrial intactness.
Therefore, it was concluded from the present results that tumor cell mitochondria did not differ essentially from normal tissue mitochondria in the respiratory control capacity and electrophoretic mobility.

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Nature of antigens of cultured Burkitt lymphoma cells, P3HR-1 line, which are continuously producing Epstein-Barr (EB) virus, was studied by means of membrane immunofluorescence. The ring type as well as diffuse type of antigens in the cells demonstrated by membrane immunofluorescence was not distinguishable from the EB virus antigen which was detected by acetone-fixed cell preparation in the following experiments: (1) Analysis of reactivity of the antigens to various human sera, (2) pattern of the antigen synthesis in cells, (3) absorption tests with a representative serum, and (4) their resistance to treatment with acetone or heat. The present studies suggested that at least a portion of the antigens of the cells detected by membrane immunofluorescence is either identical with or closely related to EB virus antigen.

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An electron microscopic study was made on the lung of male Sprague-Dawley rats given a single injection of 4-nitroquinoline 1-oxide. Nucleolar alterations characterized by disintegration of the reticular structure, and segregation of the granular and fibrillar components into separate zones occurred in the alveolar epithelial cells, both type I and type II cells, as well as in the epithelial cells lining the alveolar ducts and the terminal bronchioles. These alterations appeared prominently 6 to 12hr after injection. At the 48th hour, the reticular structure of the nucleolus appeared to be reorganized in association with an abundance of the granular component. A series of quinoline derivatives with carcinogenic activity, including 4-hydroxyaminoquinoline 1-oxide known as an active intermediate of 4-nitroquinoline 1-oxide, was found to produce these nucleolar alterations. Noncarcinogenic quinolines showed no such effect. The nucleolar alterations occurred also in the alveolar epithelial cells of mice following an injection of either 4-nitroor 4-hydroxyaminoquinoline 1-oxide.

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The survival curve of tumor cells in one-day-old solid tumors was investigated as a function of the dose of cyclophosphamide. Serially diluted tumor cells were transplanted intracutaneously into six sites on the dorsal skin of mice for TD₅₀ assay. The drug was injected intraperitoneally 24hr later when the inoculum was expected to have formed microcolonies or one-day-old solid tumors. Each TD₅₀ assay group received a different dose of cyclophosphamide. The TD₅₀ was computed from tumor-take frequencies by logit analysis. Survival fractions were calculated from the ratio of TD₅₀ of control to that of cyclophosphamide treated.
The dose-cell survival curve resembled the multi-component cell survival curve after X-ray irradiation, the cyclophosphamide-sensitive part being followed by a cyclophosphamide-resistant tail. The resistant cell fraction is discussed and a hypothesisa dvanced that a small fraction of slowly-proliferatingc ells may be present probably in hypoxic foci in one-day-old tumors. The cyclophosphamide-resistant tail in the survival curve is considered to represent the sensitivity of such tumor cells. This may mean that cyclophosphamide is incorporated into the hypoxic tumor cells.

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The magnitude of spectral change induced by hexobarbital, aminopyrine, or aniline in liver microsomes from male and female rats bearing Walker 256 carcinosarcoma was investigated. Such a change induced by all three drugs was markedly decreased in tumor-bearing male and female rats. Since the decrease in spectral change is similar to that in the activity of drug oxidation, the decrease in the substrate binding with cytochrome P-450 is assumed to be a factor responsible for the decrease in the oxidation of drugs in tumor-bearing rats.
The decrease in hexobarbital- or aminopyrine-induced spectral change in tumorbearing male rats was due to the decrease in the content of P-450 and the binding capacity of P-450 for hexobarbital or aminopyrine. On the other hand, the decrease in hexobarbital- or aminopyrine-induced spectral change in tumor-bearing female rats and that in aniline-induced spectral change in tumor-bearing rats of both sexes were due mainly to the decrease in the content of P-450.
The inability of testosterone treatment to prevent the decrease in the binding capacity of cytochrome P-450 for hexobarbital suggests that the action of testosterone to increase the binding capacity of P-450 for hexobarbital may be impaired in tumor-bearing rats.

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1) Skin tumor developed in ACI/N rats that received 3-methylcholanthrene by skin painting and that plus 4-dimethylaminostilbene in the diet.
2) Trichoepitheliomas were much more common in animals painted with 3-methylcholanthrene and basal cell carcinomas were much more common in the group with 3-methylcholanthrene painting and 4-dimethylaminostilbene.

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The mode of incorporation and binding of 4-nitroquinoline[Bz-¹⁴C] 1-oxide to hamster embryo cells (HE cells) was investigated. The carcinogen is incorporated within a short time and is bound to macromolecules of HE cells with a characteristic time course. The binding persists for 72hr after treatment. The rate of incorporation is directly proportional to concentration of the carcinogen and inversely proportional to the cell number. There is no competent cellular condition or phase in which incorporation and binding of the carcinogen occur.

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Antitumor activity of various derivatives of 5-amino-4-imidazolecarboxamide was further examined.2', 3', 5'-Tri-O-formyl-1-β-D-ribofuranosyl-5-formamido-4-imidazolethiocarboxamide (IV) was found to be quite active, and 1-β-D-ribofuranosyl-5-amino-4-imidazolethiocarboxamide 5'-phosphate was as active as the corresponding riboside, whereas thiocarbamoylamido, halogeno, and cyano derivatives of imidazole were totally inactive.
Antitumor activity and toxicity of IV were compared with those of the known active agents, 6-mercaptopurine and 9-β-D-ribofuranosyl-6-mercaptopurine. ED₉₀, LD₁₀, and therapeutic index of IV on the Nakahara-Fukuoka sarcoma system were 13, 160mg/kg/day, and 12.3, respectively, whereas they were 13, 100mg/kg/day, and 7.7 for 6-mercaptopurine, and 15, 370mg/kg/day, and 24.7 for 9-β-D-ribofuranosyl-6-mercaptopurine. Further, ILS₃₀, optimal dose, and therapeutic ratio of IV on the L-1210 leukemia system were 6.1, 50mg/kg/day, and 8.2, respectively, while they were 4.6, 30mg/kg/day, and 6.5 for 6-mercaptopurine, and 110, 300mg/kg/day, and 2.7 for 9-β-D-ribofuranosyl-6-mercaptopurine. As a result, IV was considered to be more potent than 6-mercaptopurine.

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It seems that at least one of the antitumor effects of coliphage T₂ is brought about with the DNA, the principal component of the phage.

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Intrathymic inoculation of cell-free centrifugates of the thymus from 5-month-old, non-leukemic AKR mice was highly leukemogenic in mice of AKR, C3Hf/Bi, and (C3Hf×AKR)F₁ hybrid, all homozygous for H-2^k but ineffective in mice of C57BL (H-2^bb) and DBA/2 (H-2^dd). A/Jax (H-2^aa) and (C57BL×AKR)F₁ hybrid (H-2^kb) were slightly susceptible.

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N-Methyl-bis(3-mesyloxypropyl)amine hydrochloride and cyclophosphamide were shown to be effective against L-1210 and Walker carcinosarcoma-256, and were immuno-suppressive to mice immunized with sheep erythrocytes. Bis(3-mesyloxypropyl)amine hydrochloride was also inhibitory to L-1210, C-1498, and Walker carcinosarcoma-256, but had less immunosuppressive activity. Nitromin and Myleran were almost ineffective.

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