The mutagenic action of 4-nitroquinoline 1-oxide was compared with that of 4-hydroxyaminoquinoline 1-oxide using Escherichia coli. A large proportion of phenotypic reversions induced by both compounds in amber auxotrophic strains of E. coli K12 was a suppressor mutation. The types of suppressors induced by both compounds were similar. The targets of these mutagens are discussed on the basis of the suppressor types induced.

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Long-term results of cancer chemotherapy as an adjunct to gastrectomy were investigated in 704 gastric cancer patients. A single dose of 20-30mg of Mitomycin-C was administered concentratively on the day of and the day following gastrectomy, or intermittently twice a week with a single dose of 10mg. A good response was observed in the group of concentrative administration, especially in the patients of stages III and IV. An effect of combining the allogeneic bone marrow transplantation with cancer chemotherapy should also be emphasized. Concerning the anticancer effect of the transplanted bone marrow cells the possibility of non-specific participation of anaerobic corynebacterium contained in the bone marrow was discussed.

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Synthesis, and antitumor and immunosuppressive activities of some disulfide derivatives of thiopurine have been reported. 6-(2, 6-Dichlorobenzyl)dithiopurine (AV385) and 2-amino-6-[α-(2-chlorophenyl)ethyl]dithiopurine (AV619) showed the most potent antitumor activities against leukemia L-1210. However, none of these compounds showed antitumor effect on a 6-mercaptopurine-resistant line of leukemia L-1210 (L-1210/MP).
While all of the 6-thioguanine disulfide derivatives strongly suppressed the serum antibody production to the sheep red blood cells in mice, such activity of 6-mercaptopurine disulfide derivatives was generally weak. 6-(1-Adamantyl)dithiopurine (AV 375), 6-(2, 6-dichlorobenzyl)dithiopurine (AV385), 6-[α-(2-chlorophenyl)ethyl]-dithiopurine (AV611), and 6-[β-(4-chlorophenyl)ethyl]dithiopurine (AV610) inhibited the rejection of L-1210/MP allograft in ICR mice.

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Patients who underwent gastrectomy for stomach carcinoma received one-shot injection of Mitomycin-C into the hepatic artery at the time of surgery as a prophylactic adjuvant chemotherapy. Elevation of transaminases and alkaline phosphatase, and hepatic recurrence were likely to occur in these treated patients.
Confirmatory laboratory experiments showed that an increase of metastasis formation was the most pronounced when the rat was given Mitomycin-C into the hepatic artery before inoculation of Yoshida sarcoma cells. Histological examination showed that remarkable damage of liver cells was produced after administration of Mitomycin-C into the hepatic artery. The treatment of the rats bearing multiple small metastatic nodules with Mitomycin-C was effective when the drug was given either into the hepatic artery or into the portal vein.
These findings indicate that prophylactic use of anticancer agents through the hepatic artery might be meaningless and harmful but, if micrometastases are already present, it should be effective in preventing them from growing.

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The effect of five antitumor drugs on metabolism of mouse liver catalase was studied indirectly by determining catalase activity with a combined use of 3-amino-1, 2, 4-triazole. Kanamycin, Actinomycin-J, Mitomycin-C, 5-fluorouracil, and cycloheximide were intraperitoneally injected to mice (one-half of LD₅₀ dose/kg body weight/day, 4 times). Actinomycin-J, Mitomycin-C, and 5-fluorouracil produced greater decrease in liver catalase activity, and more retarded restoration of activity than Kanamycin and cycloheximide. When aminotriazole (1.0g/kg) was injected 24hr after the last (4th) drug injection to deplete catalase present in liver, retardation of the activity recovery was evidently observed when compared with the normal recovery curve following the aminotriazole injection. A similar tendency of inhibition of catalase biosynthesis by those antitumor drugs was demonstrated by plotting the difference in activity between aminotriazole-treated and antitumor drug plus aminotriazole-treated groups vs. time.
Daily injection of smaller amounts of the antitumor drugs (Kanamycin 0.5g, Actinomycin-J 0.04mg, Mitomycin-C 1.25mg, 5-fluorouracil 3.0mg, and cycloheximide 2.0mg/kg body weight) produced approximate plateaus during 5th to 8th day of injection. Under a similar condition, aminotriazole was injected (1.0g/kg) to estimate the rates of catalase synthesis (K_S) and degradation (K_D). K_D was greatly reduced by Mitomycin-C and cycloheximide, considerably by Actinomycin-J and 5-fluorouracil, and slightly by Kanamycin, whereas K_S was more strongly lowered by Actinomycin-J, Mitomycin-C, 5-fluorouracil, and cycloheximide than that by Kanamycin. It is suggested that the decrease in K_S by the antitumor drugs is responded by reduction of K_D for autoregulation of liver catalase metabolism.

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The effect of high-protein and high-carbohydrate diets, with the same total calorie as the standard diet, and of a high-lipid diet in relatively higher calorie content on tumor growth was studied in ddI, dd/OS, and Swiss albino mice which were inoculated with sarcoma-180 cells or Ehrlich carcinoma cells subcutaneously into the axillary region or intraperitoneally. While the mice after the intraperitoneal transplantation of sarcoma-180 cells survived without any apparent difference under different dietary regimens, much different responses of tumor growth to the dietary modification were observed in the mice inoculated with the tumor subcutaneously. The high-carbohydrate diet, i.e., a diet with 12% milk casein content, yielded continuous growth of sarcoma-180 cells in the ddI and Swiss albino mice but not in the dd/OS mice. However, spontaneous regression of subcutaneous tumors was observed in all the mice fed on the standard diet, i.e., a diet with 25% milk casein content. Tumor regression in the subcutaneous form was seen in some mice bearing sarcoma-180 cells when fed a high protein diet, i.e., one with a 60% milk casein content or a high lipid diet, i.e., one with a 30% safflower oil-linolic acid content.
On the other hand, in all the ddI mice bearing Ehrlich carcinoma cells subcutaneously, no modification of the tumor growth was shown through dietary manipulation. However, a slight extension of their survival time was observed after the intraperitoneal inoculation of the tumors in some of the mice fed on a high-protein diet, compared to the survival time of the mice fed on a high-carbohydrate diet.

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Increase in type M₂ pyruvate kinase activity in the liver of 11 strains of mice was examined after the transplantation of Ehrlich ascites tumor cells. A similar increase in low K_m hexokinase activity was also found in the liver of tumor-bearing mice. These increases in both type M₂ pyruvate kinase and low K_m hexokinase activities in tumor-bearing animals appeared more clearly in the strains which showed lower activities in the control animals than the ones which showed higher activities. The type M₂ pyruvate kinase activity was also increased by the intraperitoneal injection of the extract of sonically disrupted tumor cells. Considering the result of the ultrafiltration experiment with a Diaflo membrane, the active factor in the tumor extract seems to have lower molecular weight than 50, 000.

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Pulmonary tumors were induced in A/Jax strain of mice by a single injection of 3-methylcholanthrene and the tumors were transplanted into subcutaneous region of isologous hosts. Thus, five transplantable tumor lines were established. The tumors progressed gradually from benign to malignant during such processes.
Five ascites tumors were derived from the transplantable lines and were further brought into in vitro culture. Examinations of these tumors by electron microscopy revealed the presence of intracisternal A-type and C-type virus-like particles. These data suggested that the amount of intracisternal A and C particles increased in the following order: Type-B cell of normal lung, primarily induced pulmonary tumor, subcutaneously transplantable pulmonary adenocarcinomas, intraperitoneal solid tumors of the ascites lines, ascites tumors, and the in vitro cultured cells.

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Hepatic tumors were induced in the Sprague-Dawley rats at an exceptionally high incidence by continuous administration of a heavy dose (10mg/kg/day) of cycasin. Induction time ranged from 167 to 556 days. The hepatic tumors were either hepatomas or hepatic sarcomas. Both types were produced in about the same ratio.

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Antigenic components of a rat ascites hepatoma AH-272 strain were compared with those of normal rat liver tissue by the precipitation reaction in agar gel, and an antigen which was characteristic of tissues other than the tissue of origin of the tumor was demonstrated to be present in the soluble extract of the hepatoma cells. The content of the antigen in normal rat tissues and in several strains of rat ascites tumor cells was quantitatively determined. Localization of the antigen in the tumor cells was investigated by fluorescent antibody method and by cell fractionation, and was revealed to be in soluble structure of the cytoplasm. The antigen was purified and finally separated in crystalline form, and characterized physicochemically as a protein with molecular weight of 40, 000 to 50, 0000.

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As a relatively simplified model for the study of glycoproteins in relation to experimental cancer from a point of tumor-host relationship, experiments were carried out with Donryu rats bearing subcutaneous AH-109A tumor and basic data were obtained. In rats given implants of AH-109A cells, significant increases in serum protein-bound hexoses, hexosamines, and sialic acid occurred in parallel with tumor growth. These changes could be accounted for almost exclusively by the elevation of seromucoid-bound carbohydrate level. Significant increase of α-globulin occurred during tumor growth. It was suggested that an increase of α-globulin greatly contributed to an increase of total serum protein-bound carbohydrates. As to β-globulin, although there was no change in the quantity of protein moiety, there was a relative increase of carbohydrate-rich proteins. Autopsy confirmed that liver metastasis was negligible.
In addition, daily cycle of seromucoid level and the effect of fasting and refeeding on seromucoid level in normal rats were observed.

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A plasma iron-depressing factor was purified from Rhodamine sarcoma. The purification procedure consisted of extraction with water, dialysis, column chromatography over Amberlite XE-64 and ECTEOLA-cellulose, and gel-filtration over Sephadex G-200 column. The purified substance was obtained in 0.018% yield from an acetone-dried powder of Rhodamine sarcoma. The final preparation caused reduction of the plasma iron level at a dose of 2.5μg/rat, but did not affect mouse liver catalase activity. This indicates that the factor depressing plasma iron is distinct from that depressing liver catalase. The activity of the plasma iron-depressing factor was not affected by heat treatment, but was lost on ashing or treatment with hydroxylamine. It was demonstrated that rat liver contains an enzyme inactivating the plasma iron-depressing factor.

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Bovine adenovirus type-3 was inoculated subcutaneously in hamsters of various ages from 1 to 95 days. Tumors developed in many hamsters of every age group. When the virus was inoculated into animals younger than 14 days, two types of tumor, differentiated and undifferentiated, developed at the site of injection, which grew non-progressively and progressively, respectively. In animals older than 21 days, undifferentiated type of tumor developed and its growth was of non-progressive type. Such growth behavior of the tumors seemed to depend on the age-dependent resistance of the host to tumor growth.

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Effect of cryosurgical freezing on the growth of C3H mouse mammary carcinoma was investigated. The growth was inhibited and the cure rate of the tumor increased in accordance with the number of treatments.

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Epstein-Barr virus-related antigens in Burkitt lymphoma cells were analysed by peroxidase labeled antibody method. The result indicated that immunofluorescence-positive human serum does not contain the antibody against Epstein-Barr virus capsid but contain viral envelope.

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The immunocapability of primed lymphoid cells was greatly suppressed when the cells were cultured in recipient mice pretreated either with nuclear fraction of Ehrlich ascites tumor cells or cell-free cancerous ascites. The chromatin fraction prepared from the nuclear fraction showed immunosuppressive activity comparable to that of the nuclear fraction.

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Carcinogenicity of butyl(3-carboxyproplyl)nitrosoamine (BCPN), a principal urinary metabolite of butyl(4-hydroxybutyl)nitrosoamine (BBN), was tested in male ACI/N rats by oral administration. It was demonstrated that BCPN is a potent and selective urinary bladder carcinogen as is the original compound BBN.

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4-Nitroquinoline 1-oxide (I) and related compounds lowered the viscosity of DNA solution at above 60°. 4-Hydroxyaminoquinoline 1-oxide (II) was the most effective. I was converted into II when incubated with DNA at 37°. It was concluded that 4-hydroxyaminoquinoline 1-oxide produced a chain breakage in DNA at elevated temperatures.

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The fractionated treatment of L5 cells at 5-hr intervals yielded a simple exponential survival curve instead of upward concave curve. The finding suggests that the fractionated treatment given at an adequate interval sterilizes tumor cells more efficiently than the continuous treatment.

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