Electronic structure of 4-dimethylaminostilbene and its related compounds is obtained using the frontier electron method. The comparison of the electron distribution with the anti-tumor activity is made and a correlation between the approximate superdelocalizability for nucleophilic attack (S'^(N)) at position 2, dimethylaminonitrogen and α-carbon atom and the anti-tumor activity of these compounds is found. In view of this finding, the importance of nucleophilic reactivity for an ability to inhibit tumor is stressed and some discussions on the coexistence of carcinogenicity and anti-tumor activity in one and the some compound are made on the basis of electronic structure and chemical reactivity. A guiding principle for searching for the anti-tumor compounds is proposed from the point of view of the electron distribution or chemical reactivity of 4-dimethylaminostilbene derivatives and other tumoricidal compounds, and it is stated that the synthesis and screening of quinone derivatives are recommended to be operative.
This investigation was supported in part by a grant-in-aid from the Educational Ministry of the Japanese Government.

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Separation of the high molecular weight components of gastric juice on a column of Dowex 50 X-8 has been described. Results obtained by applying the method for normal control gastric juice were compared with those obtained by analyses of carcinomatous gastric juice and of non-carcinomatous histamine-refractory achlorhydric gastric juice.
1. Seven different protein fractions have been obtained by this method.
2. Of the two main polysaccharide-containing fractions, P-I and P-III, neither was proved to be free of protein. Paper chromatography of gastric juice also was sufficient to exclude complete separation of polysaccharide and protein.
3. In the chromatogram of carcinomatous gastric juice, a noteworthy increase in hexose content and a decrease of tyrosine content were found to occur. P-III also was found to be similarly changed, and polysaccharide components found in P-V of the control specimen was found to be absent in carcinomatous sample. The above finding may suggest qualitative and quantitative alteration of mucoprotein and mucoproteose components of gastric juice in the presence of gastric carcinoma.
4. Histamine-refractory achlorhydric gastric juice selected from patients with chronic gastritis and chronic or recurrent gastric ulcer showed a chromatogram having a character intermediate between the control and the carcinomatous gastric juice. However, increases of polysaccharide components other than hexose in P-I was not so remarkable as was observed in carcinomatous gastric juice.
5. High polarographic activity was observed in P-I of all samples examined, the activity in carcinomatous specimen being the strongest of all. P-III of carcinomatous sample was also found to have a remarkably strong polarographic activity.
6. Strongly increased contents of polysaccharide components, including SA, in P-I and P-III of carcinomatous gastric juice may suggest the possibility of biochemical diagnosis of carcinoma of the stomach with DPA reaction.
7. Possible significance of histamine-refractory achlorhydria among chronic gastric disorders as a fucntional pre-carcinomatous stage of the stomach was discussed.

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1) Gastric juice of patients with carcinoma of the stomach was found to have low peptic activity. Non-carcinomatous histamine-refractory achlorhydric gastric juice after stimulation with insulin was found to be often accompanied with increase in pepsin.
2) Pepsin present in gastric juice was detected as a combination of two peaks when tested with continuous electrophoresis. The minor peak having an electrophoretic mobility of B₂ was thought to be pepsinogen, whereas the major pepsin peak having a mobility faster than B₁ was probably an interaction product between pepsin and gastric juice protein, according to the result of crossing electrophoresis.
3) Pepsin was found to appear in P-I fraction when gastric juice was subjected to cation exchange chromatography.
4) Carcinomatous gastric was found to contain increased amounts of blood group substances. This was not the result of simple contamination with bleeding. Cation exchange chromatography of gastric juice revealed that carcinomatous gastric juice was characterized by a specific increase of blood group activity in P-V.
5) Both continuous paper electrophoresis and cation exchange chromatography were available for complete separation of KIK factor and toxohormone. The significance of chemical change in corresponding fractions for the diagnosis of cancer was discussed.

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1) With the use of the original strain and subline of the Yoshida ascites sarcoma and ascites hepatoma, AH 13 and AH 7974, resistant to Methyl-bis-(β-chlorethyl)-amine N-oxide (MBAO), sulfhydryl content of tumor cells was determined according to the amperometric titration. No significant difference was observed in the total sulfhydryl content between resistant subline and original strain. However, tumor cells in the MBAO-resistant subline contained a larger amount of non-protein sulfhydryl group than those in the corresponding original strain, whether the Yoshida ascites sarcoma or ascites hepatoma. Since MBAO shows an affinity to sulfhydryl group, it seemed to be most probable that tumor cells containing a large amount of nonprotein sulfhydryl group are more resistant, owing to counteracting the action of the agents, than those containing a smaller amount.
2) Comparing the susceptibility to MBAO of tumor cells in original strains, the Yoshida ascites sarcoma, AH 13, AH 130, AH 602, and AH 7974, it was confirmed that the order of decreasing resistance is AH 7974, AH 602, the Yoshida ascites sarcoma, AH 13, and AH 130, i.e., AH 7974 was the most resistant and AH 130 the most sensitive to MBAO. Sulfhydryl content of tumor cells in these original strains was determined, but no correlation was observed between the susceptibility to MBAO and sulfhydryl content of tumor cells in original strains.
3) From these results, comparison of the mechanism of acquired resistance developed through the use of a certain anti-tumor agent and that of natural resistance was made.

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The present article deals with some cytological effects of Thio-TEPA and Actinomycin-C on cells of mouse fibroblasts and of CBA mouse mammary adenocarcinoma both in culture, with special reference to the morphological and cytochemical analyses of drastic response.
Thio-TEPA induced 1) the loss of stainability of the nuclear material with May-Grunwald-Giemsa, and 2) severe clumping, fragmentation and translocation of metaphasic chromosomes and sticky bridges at ana- and telophase. The changes seem to be an indication of alteration in the nature of DNA. Cytoplasmic damage is less intensitive as compared with the nuclear damage.
Actinomycin-C caused 1) unusual distribution of the substances of the nucleus, cytoplasm and nucleolus, 2) swelling, deformation and fragmentation of the nucleus, and 3) aggregation of some basophilic substances in the cytoplasm. Above features suggest the possibility of changes in DNA as well as in RNA.
Evidence was presented with culture material that there were some cells which remained undamaged by the drug applied. Such cells seem to cause the regrowth of the tissue by proliferation in the agent-free medium.

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This study deals with immunologic specificity of two sublines, C and D, of the Yoshida sarcoma, with reference to their homotransplantability, use being made of rabbit antisera prepared against two cellular components of tumor cells.
The anti-nucleoprotein antisera prepared from tumor cells of one subline gave an intensive cytotoxic- and agglutinin-reaction to antigen cells of the same subline, but were rather weak in reaction to cells of the other subline. Block titrations with anti-ethanol-extract antisera showed a precipitin reaction pattern which differed between different antigen-extracts derived from the two sublines.
The homotransplantability of the two subline-tumors was nearly identical to Wistar rats, but different to Buffalo rats and its interstrain hybrids.
The above findings may support the view that the two sublines of the Yoshida sarcoma here considered are characterized by their own antigenicity, different from one another.

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The acid hematein lipoprotein staining was applied on non-neoplastic and neoplastic human uterine biopsy specimens. It was found that epithelial cells and neoplastic cells of epithelial origin reacted differently to acid hematein test, the former being definitely positive and the latter negative. The non-neoplastic epithelial cells lying near the epithelioma are sometimes negative in reaction.
This staining method may serve to supplement prevailing conventional cytological and histological methods in biopsy diagnosis of uterine epitheliomas.

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1) The rats which had been injected at birth with 1.2mg of p-dimethylaminoazobenzene have shown no abnormality either in the hepatocarcinogenesis or in the general conditions later in life.
2) As to the sexual difference in the DAB hepatocarcinogenesis the present experiment suggested the following two facts:
a) In the "process of cell cancerization" in the rat liver, there was no essential difference between in male and in female, but, b) in the "process of clinical manifestation" of the evoked cancer cell(s), there was a remarkable difference between the sexes; much shorter period was required in male than in female. In other words, female hosts required much longer period of time to establish the clinical tumors.
3) The previous studies concerning the sexual difference in the azo dye carcinogenesis as well as the so-called two phase mechanism in the experimental carcinogenesis were discussed.

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The depression of ATP level by nitroquinoline derivatives was counteracted completely by the addition of nicotinamide. The inhibition of ³²P incorporation into the RNA by nitroquinoline derivatives was also partially deleted by nicotinamide. However, the inhibition of amino acid incorporation into protein by nitroquinoline derivatives was entirely unaffected by nicotinamide. It was concluded from these results that there were at least two different action sites of nitroquinoline derivatives in Ehrlich cells: one related to glycolysis and the other to protein synthesis.

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1. By the injection of 4-nitroquinaldine N-oxide, the DPN level in tumor tissue was suddenly and markely decreased, but the liver DPN level was only slightly and very slowly reduced.
2. The DPN synthesizing enzymes in tumor and liver were reduced by the administration of nitroquinaldine. The activity of DPNase was not altered by the injection of the compound.
3. The effect of nitroquinaldine on DPN level in partially hepatectomized rat liver was not different from that in normal intact liver.
4. It was suggeted that 4-nitroquinoline N-oxide and its derivatives may be inhibitors of protein synthesizing system.

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The anaerobic glycolysis by mitochondria has been studied in normal mouse liver and various tumors (Ehrlich ascites carcinoma, spontaneously developed mouse mammary cancer and lymphosarcoma) with the following results:
(1) Normal mouse liver and various tumor mitochondria were found to be able to convert glucose into lactic acid under the anaerobic condition, with differences in the degree of glycolytic activity. But higher rates of glycolysis by tumor mitochondria than by normal mouse liver mitochondria were not observed.
(2) The lactic acid production of normal and tumor cell mitochondria increased obviously by the addition of boiled supernatant fraction which has been enzymatically inactivated. In this case, among the same tissues, the lower the lactic acid production by mitochondria alone was, the greater the rate of increase of their lactic acid production tended to be.
(3) The negative mutuality has been found between the lactic acid production by mitochondria added with boiled supernatant fraction and the lactic acid production by supernatant fraction.
(4) No specificities were found in the glycolysis-promoting effect of boiled supernatant. This effect was found for both mitochondria and supernatant fraction. The effective factors on glycolysis in boiled supernatant fraction are presumed to be nonproteinic and non-enzymic.
(5) The glycolysis by mitochondria is promoted by the addition of insulin, while that by supernatant fraction showed the tendency to decrease by the addition of insulin. This result showed that the glycolytic mechanisms of mitochondria and supernatant fraction are principally different and it is presumed from this consideration that the glycolytic enzyme systems of mitochondria in cells performed the functions closely related to the definite structural organization similar to the respiratory enzyme systems.

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