The distribution of N-methyl-N'-nitro-N-nitrosoguanidines (MNNG) in various organs of rats and the in vivo incorporation of the radioactivities of MNNG into DNA and histone in rat tissues were studied using MNNG[guanidino-¹⁴C] and MNNG[methyl-¹⁴C]. Radioactivity from MNNG[guanidino-¹⁴C] was mostly found in the stomach and intestine while that from MNNG[methyl-¹⁴C] was detected not only in the stomach and intestine but also in the liver and kidney. In the glandular stomach, radioactivity from MNNG[guanidino-¹⁴C] was incorporated into histone and that from MNNG[methyl-¹⁴C] into both DNA and histone, especially in the former. In the liver, however, radioactivity from MNNG[guanidino-¹⁴C] was not detected in histone but DNA was labeled with radioactivity from MNNG[methyl-¹⁴C].

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Anti-EA, the antibodies against early antigens (EA) induced by Epstein-Barr (EB) virus, was titrated in 244 sera of 190 patients with nasopharyngeal carcinoma (NPC), and of the control groups; 45 patients with other ear, nose, and throat (ENT) diseases, 107 patients with cancer outside the head and neck region, and 101 healthy people. The results revealed that the geometric mean titer (GMT) of anti-EA in patients with NPC was high (1:93.5), and the positive rate of that was also significantly higher than those of the control groups (88.1%). The positive rate of anti-EA in NPC patients before treatment (88.8%) was about the same as that after treatment (84.1% to 86.6%), but higher in patients with recurrence (100.0%). On the other hand, GMT reduced to 1:68.3 and 1:72.9 in patients after treatment, although it was 1:111.8 in patients before treatment, and rose to a significantly high level, 1:166.6, inpatients with recurrence. Meanwhile, patients with some other ENT diseases and malignancies also showed higher incidences of positive rate (5.6% to 18.2%) than that of healthy people (2.0%), but these were still far less than that of NPC patients. The results suggested that the anti-EA may be associated with the progress of NPC.

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The effect of concanavalin-A on the aggregation of 4-(dimethylamino)azobenzene-induced rat hepatoma cells, dRLa-74 and dRLh-84, which have a low and high tumor-producing activity, respectively, was examined in rotation-mediated cell culture. Concanavalin-A had a moderate concentration-dependent effect on the aggregation of dRLa-74 cells. At the concentration of 0.01% concanavalin-A was effective in inhibiting the aggregation of dRLa-74 cells to about two-thirds of that of the control cultures in their mean diameter. Concanavalin-A also had a concentration-dependent effect on the aggregation of dRLh-84 cells, but its effect on dRLh-84 cells was stronger than that on dRLa-74 cells. In the presence of 0.01% of concanavalin-A the mean diameter of aggregates of dRLh-84 cells was about one-fifth of that in the control cultures.

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Effect of the concurrent administration of salts of heavy metals such as copper, manganese, zinc, and nickel, in suppressing hepatocarcinogenesis by 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB) in rats was examined and, in order to find the mechanism of this suppression, effect of these metal salts on the formation of protein-bound dye in the liver and hepatic activity to metabolize 4-(dimethylamino) azobenzene (DAB) was examined. Carcinogenesis of 3'-Me-DAB was inhibited most markedly by a copper salt, followed by manganese and nickel salts. No such effect was observed with the zinc salt. The effect of these metal salts in suppressing azo-dye carcinogenesis seemed to parallel their capacity to reduce the hepatic level of protein-bound dye and to enhance the hepatic azo reductase activity. No correlation was found between this suppressive effect of these metal salts and their effect on other enzymic activities related to aminoazo dye metabolism such as ring hydroxylation and oxidative N-demethylation. The present results seemed to indicate that the increased azo reductase activity in the rat liver by the concurrent administration of copper and other salts results in narrowing of other metabolic route related to the metabolic activation of the dye which is responsible for the carcinogen binding to proteins and henceforth to hepatocarcinogenesis.

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Mice given 7, 12-dimethylbenz[a]anthracene (DMBA) simultaneously with immunization with bacterial α-amylase (BαA) showed an augmented anti-BαA response in sera as compared with those of mice given only BαA, but the development of immunological memory in DMBA-treated mice was constantly and persistently depressed. Administration of syngeneic normal thymocytes to DMBA-treated mice further strengthened the augmenting effect of DMBA on the serum antibody titers, whereas administration of thymocytes to normal mice not treated with DMBA revealed rather suppressive effect on the serum antibody titers. It was also found that most of mice given both DMBA and normal thymocytes suffered from a variety of wasting symptoms resembling those of runt disease or graft-versus-host reaction, and many of them died within 4 to 5 weeks. Histological examination showed almost complete loss of follicular organization in spleen and lymph nodes. A similar but slight histological change was observed in mice given only DMBA. These findings suggest that the immune system of mice was markedly disturbed by the administration of DMBA and normal thymocytes.

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Five human floating cell lines, P3HR-1, QIMR-WIL, OAT, C-6, and Daudi, were examined for susceptibility to superinfection with Epstein-Barr (EB) virus produced from the P3HR-1 cells. Formation of EB virus-associated early (E) antigen inducible by treatment with 5-iododeoxyuridine was demonstrated in the four cell lines but not in the QIMR-WIL line. The P3HR-1 cells had no capacity of adsorbing the virus, while other four lines showed adsorption of the virus. The infected OAT and C-6 lines yielded E antigen-producing cells but only few viral capsid (VC) antigen-producing cells. Both E and VC antigens were demonstrated in about the same number of cells in the infected QIMR-WIL and Daudi lines. The percentage of antigen-positive cells in the Daudi line was much higher than that of the QIMRWIL line. This result suggests that the Daudi line was the most permissive in the five cell lines responding in different modes to superinfection by EB virus.

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The antitumor activities of nine new methanesulfonates of aminoglycols were evaluated. Two compounds, 3, 3'-(morpholinopropylimino)-di(1-propanol) dimethanesulfonate (ester) dihydrochloride (No. 888) and 3, 3'-(dibutylaminopropylimino)-di(1-propanol) dimethanesulfonate (ester) dihydroehloride (No. 893), showed marked activities against rats bearing Yoshida sarcoma. These two compounds cured 70-80% of the treated rats at their optimal doses. On the ascites hepatomas, when the tumor was inoculated intraperitoneally and the drug was given by the same route, 3, 3'-(methylimino)-di(1-propanol) dimethanesulfonate (ester) diphenyldisulfonate (No. 838D) was better than No. 888 or 893. However, when the tumor was intravenously inoculated and the drug was intraperitoneally given, or when the tumor was intravenously inoculated and the drug was given by the same route, a clear difference in their activities was observed. No. 838D was the most active against AH-272 and Nos. 888 and 893 against AH-66, but No. 893 was less active than No. 888.

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The heterogeneity pattern of catalase in Morris hepatomas 7316A, 7800, 5123C, 7794A, 9618A, 16, and 9618B was examined by isoelectric focusing using Ampholine-carrier ampholyte and DEAE-cellulose column chromatography. Catalase in the liver of normal adult rats was fractionated by isoelectric focusing into 5 major components each having its own isoelectric point at pH 6.95, 6.75, 6.50, 6.10, and 5.90. In all the hepatomas examined, the acidic components of catalase having isoelectric points at pH 6.10 and 5.90 were found to disappear, while basic components of the enzyme showed a definite appearance. Chromatographic analysis of the enzyme using DEAE-cellulose column showed that a considerable portion of the enzyme activity failed to be adsorbed on the ion exchanger, which may well support the above-mentioned appearance of the basic components of the enzyme. The isoelectric focusing pattern as well as the chromatographic elution characteristics of catalase in the hepatomas closely resembled those in the liver of fetal and newborn rats. It is suggested that the alteration in the heterogeneity of hepatomas may be ascribed to the dedifferentiating nature of cancer.

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Virus-like particles, having three layers with radial nucleoids, were rarely observed in the primary tumor induced by adenovirus type-12 in hamsters as well as in the normal lung and brain tissues of newborn hamsters. On the other hand, they were detected in a large number in the transplanted tumor cells. Virus-like particles were usually found in the rough-surfaced endoplasmic reticulum, and intranuclear particles and the peculiar pattern of intracisternal budding were observed. The fine structures, location, and significance of virus-like particles were discussed.

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The colloidal iron-stained sialoglycoprotein layer on the cell surface of three different lines of transplantable Friend virus-induced tumors in rats which showed different growth patterns in the host rats was studied under the electron microscope. A relationship was found between the thickness of the iron-stained layer on the cell surface and the growth pattern of the tumors. The sialoglycoprotein layers on the cell surfaces were highly stained in WFT-2N cells which showed lethal growth in normal syngeneic rats, moderately stained in WFT-2A cells, which showed temporary growth, and weakly stained in WFT-3 cells which showed no growth. The significance of these findings in regard to the rôle of cell surface sialoglycoprotein in the masking phenomenon of tumor antigens is discussed.

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Distribution of Bleomycin-A₅ in rat organs and tumors after its intravenous administration and the antitumor effect of Bleomycin-A₅ were studied. Bleomycin-A₅ showed a higher concentration than Bleomycin-A₂ in mammary gland and stomach, and showed inhibition against rat mammary carcinoma induced by 7, 12-dimethylbenz [a]anthracene. Further, Bleomycin-A₅ showed some effect in reducing the size of human mammary adenocarcinoma.

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Mixed lymphoctye-tumor cell culture test was performed before and after surgery. Significant elevation of the reactivity of lymphocytes to cancer cells was observed in the test performed after surgery, but not before surgery. This indicated that the surgical removal of tumor might favor the host's defense against cancer

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The modal chromosome number in cells of two sublines and their original line was hypotriploid. Five marker chromosomes were confirmed in two sublines, but six marker chromosomes were identified in their original line. Karyological differences were manifested in two sublines and their original line.

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Based on quantitative analysis of the interaction of Epstein-Barr virus (P3HR-1 strain) and C-6 lymphoblastoid cell line, an assay method for infectivity of the virus by immunofluorescence to detect the early antigen-forming cells was proposed.

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The capacity of various benz[a]anthracene derivatives to damage chromosomes of bone marrow cells was studied and compared with sarcoma incidence following the intramuscular injection of these compounds in the rat. The considerable parallelism between the two capacities demonstrated suggests that chromatid rearrangement underlying breakage is concerned with carcinogenesis.

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Brain tumors were induced in 50% (7/14) of adult monkeys 20-40 days after intracerebral inoculation of chicken sarcoma cells producing Schmidt-Ruppin strain of Rous sarcoma virus (SR-RSV). The tumors resembled giant-celled glioblastoma, carried SR-RSV in masked form, and contained S100 protein.

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Enhancement of hepatoma production was observed in the rats which were prenatally administered diethylnitrosoamine and postnatally fed the same carcinogen. The carcinogenic effect was especially marked in the females. Development of the hepatoma was detected by the appearance of serum α-fetoprotein.

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