Carcinoids and adenocarcinoma of the glandular stomach, analogous to those in man, were found in the chemically treated and control groups of Praomys (Mastomys) natalensis. The tumors were similar to the ones occurring spontaneously in this unique species. Adenocarcinoma of the pyloric and antral regions developed irrespective of treatment but of the fundic region only in the chemically treated group.

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A total of 81 individuals, including 41 breast cancer patients, 20 patients with other types of malignant tumors, and 20 normal volunteers, were studied in order to evaluate whether leucocyte reactivity directed to soluble tumor-associated antigens could be increased by extensive cell washings and could be blocked by preincubation with autologous serum. When 41 leucocyte samples were pretreated with autologous serum, washed 3 or 6 times, mean percentage of leucocyte adherence inhibition difference between control extract and breast cancer extract were -2.4±2.0, 5.8±1.3, and 10.0±1.2, respectively.
The results of cells preincubated with serum were significantly different from those of cells washed 3 times and 6 times (both P<0.001 by Student's t-test). The results of cells washed 3 times were significantly different from those of cells washed 6 times (P<0.05 by Student's t-test). Serum blocking factors correlated with tumor burden and clinical stage. However, leucocyte reactivity against breast cancer extract did not correlate with tumor burden or clinical stage in breast cancer patients.

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Yoshida sarcoma cells contain a factor that stimulates thymidine kinase activity in the liver of mice in vivo; intraperitoneal injection of an extract from Yoshida sarcoma into normal mice stimulated their liver thymidine kinase activity 2- to 3-fold, whereas injection of a crude extract of normal rat liver did not stimulate the activity at all.
A factor that stimulates the de novo synthesis of thymidine kinase in the liver was partially purified from Yoshida sarcoma by ammonium sulfate fractionation, DEAE-cellulose column chromatography and gel filtration. It appeared to be thermolabile and sensitive to trypsin treatment. These results suggested that it was a high-molecular weight protein. Intraperitoneal injection of this factor into 67% hepatectomized rats stimulated thymidine kinase activity 2- to 3-fold. Increase of liver thymidine kinase activity after injection of the factor into mice was blocked by simultaneous injection of actinomycin-D. These results suggest that this factor stimulates de novo synthesis of thymidine kinase in the liver.

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Metabolites of 3-methylcholanthrene in tissues and excreta of rats and mice were extracted, directly or after removal from conjugation, with ethanol or ethyl acetate, purified by Sephadex LH-20 column chromatography, and examined by gas chromatography-mass spectrometric analysis. Data from the present experiments showed that the extracts after chromatographic purification were contaminated with some tissue-derived sterols such as cholesterol. As compounds related to 3-methylcholanthrene, a dehydro compound, 1- and 2-hydroxy compounds, 11-phenol and two other phenols were identified in the extracts. Ketones and cis-1, 2-dihydroxy compounds were also detected on occasion. Some trihydroxy compounds were suggested. This is of interest because the trihydroxylated metabolites have been pointed out as precursors of ultimate carcinogen of MC recently. The high sensitivity of the lung to MC carcinogenesis was not interpreted only by specific distribution in tissue of metabolites of the hydrocarbon.

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The immunosuppressive effect of 5'-deoxy-5-fluorouridine (5'-DFUR, Ro 21-9738) was examined for both humoral and cell-mediated immunity in mice in comparison with that of 5-fluorouracil and Ftorafur (FT-207). By both oral and intraperitoneal administration, 5'-DFUR was found to be much less suppressive than 5-fluorouracil and FT-207 in all immune responses tested; hemolysin plaque-forming cells, serum hemolysin titer, delayed-type hypersensitivity and allogeneic tumor rejection. Furthermore, 5'-DFUR did not induce any reduction in either the spleen weight, thymus weight, total spleen cell number, or peripheral leucocyte number.

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Carcinogenic activity of benzo[a]pyrene alone was tested for the induction of lung cancer in rabbits. Rabbits received intrabronchial instillation of 5 or 40mg of benzo[a]pyrene suspended in sterile saline every 10 to 14 days. Cancer incidences were approximately 42% of the rabbits that survived for more than 300 days. These cancers included squamous cell carcinoma, adenocarcinoma, undifferentiated cell carcinoma, fibrosarcoma, and mixed type. In the same experiment amyloidosis was seen in 16 rabbits.

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Various tumorous ascites inhibited the antibody-dependent macrophagemediated tumor lysis in vitro (ADMC) which had been found in a C3H/He mouse-MM46 tumor system. This inhibition of ADMC was due to functional depression of effector macrophages, evidenced by in vitro and in vivo pretreatment of effector cells with ascites lipoprotein. Ascites lipoprotein also had direct cytotoxicity against various cells, but in the ADMC system, two activities appeared separately; lower concentrations of lipoprotein caused inhibition of ADMC and higher one caused cytotoxicity to macrophages and tumor cells. The component of lipoprotein active in these two activities was the lipid moiety.
These results suggest that lipoprotein in tumorous ascities depresses the function of macrophages resulting in the inhibition of ADMC and that lipid moiety is the essential component.

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An epithelial cell line, NuE15-1, was established from the liver of a 24-week-old human fetus. The cells had round clear nuclei with clear (agranular) cytoplasm of polygonal shape and grew in a pavement-like manner. The karyotype was human and heteroploid. α-Fetoprotein and α1-antitrypsin were detected in the concentrated culture medium but albumin was not. This may indicate the hepatocytic origin of the cell line. Malignant transformation was confirmed by xenotransplantability to nude mice. When inoculated intraperitoneally, the implanted cells caused lethal peritonitis carcinomatosa in 9 out of 10 mice within 3 weeks and liver metastasis was observed in one case. A possible role of α-fetoprotein-producing cells as precursors of tumor cells in hepatocar-cinogenesis is discussed.

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The cytotoxic effect of 60-F, a subcellular fraction obtained from 0.5∼0.6 saturation of cell-free extract of live hemolytic streptococci (Su-strain) with ammonium sulfate on Ehrlich ascites carcinoma cells was studied by the assay of incorporation of nucleosides and amino acid, and by the in vitro-in vivo cytocidal experiment. Additionally, the cytolytic effect of 60-F was examined by the assay of RNA and DNA released from the tumor cells. It was found that the tumor cells treated with 60-F did not take up thymidine, uridine, or leucine, that 60-F eradicated the transplantability of tumor cells in mice, and that 60-F released RNA but not DNA from the tumor cells.

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Polypoid carcinoma in the gastric antrum of a Beagle dog induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was sequentially studied by endoscopy and biopsy. Ulcer appeared on the angulus of the stomach at the 28th week and resulted in ulcer scar at the 42nd week. A new depression with atypical glands arose on the ulcer scar at the 69th week, developed elevated border at the 77th week, and progressed to a polypoid lesion at the 90th week. Well-differentiated adenocarcinoma in situ was found in the polypoid lesion at the 97th week. It gradually grew with nodular change of its surface. However, the carcinoma was ulcerated at the 126th week, became an elevated lesion with central depression at the 138th week, and finally regressed at the 154th week. At necropsy on the 202nd week, no carcinoma was found in the stomach.

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Male and female F344/DuCrj rats were given 400ppm solution of 1-propyl-1-nitrosourea continuously in their drinking water. The incidence of digestive tract tumors was as high as 32/36 (89%) and 33/39 (85%) in male and female rats, respectively. Among these, duodenal tumors were induced most frequently, and most of them were adenocarcinoma followed by adenomas and hemangiogenic tumors. Thymomas were found in 27 (75%) males and 14 (36%) females. The lymphocytic type thymoma was the most frequent, and epithelial or mixed types were found only in 8 females. Other tumors induced were mainly in the ear ducts and lung, and the incidence was less than 13%.

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Distribution of 5-fluorouracil (5-FU) in various tissues including transplanted tumors was examined 1, 3 (or 4), and 24hr after a single oral dose of 5'-deoxy-5-fluorouridine (5'-DFUR), Ftorafur (FT-207), or 5-FU itself to groups of mice bearing sarcoma-180 and of rats bearing Walker carcinoma-256. The levels of 5-FU derived from 5'-DFUR were highest in the tumors among the tissues examined 3 (or 4) and 24hr after administration. At the 1st hr after dosing the 5-FU level in the small intestine was close to, but that in other tissues was much lower than, the 5-FU level in the tumor of both types. Such a selective distribution of 5-FU in tumor tissues was not observed after dosing of either FT-207 or 5-FU itself. Since the anticancer effect of 5'-DFUR is likely to be manifested after its conversion to 5-FU, the 5'-deoxyribose moiety of 5'-DFUR may be deemed as an efficient carrier by which the 5-FU moiety is conveyed selectively to cancer tissues.

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The effect of aprotinin (Trasylol), a broad-spectrum inhibitor of proteinase, was studied on the growth of murine squamous cell carcinoma induced by 3-methylcholanthrene. In this tumor system, the administration of aprotinin was therapeutically effective. Histologically, aprotinin-treated tumor showed a significant hyperkeratosis.

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In order to evaluate directly in vivo the extent of correlation existing between mutagenic-carcinogenic activity of diazoalkanes and their DNA damaging activity, alkaline elution was used to study the induction of single-strand breaks in and repair of DNA from mice treated with N-diazoacetylgylcine amide (DGA). A dose-dependent DNA fragmentation was present, 4hr after ip injection of single doses of DGA, in liver, lung, kidney, spleen, thymus, and bone marrow. The differences among these organs in the amount of DNA damage were small, even if sometimes statistically significant. Elution profiles indicated that a progressive conversion of alkali-labile sites to single-strand breaks took place in the first 50min of elution. Twenty-four hr after treatment with 1000mg/kg, DNA damage was only slightly reduced in liver, lung and bone marrow. A detailed statistical analysis of the variability of experimental results is reported in order to give information about the reliability of the method, and to allow the possibility of calculating the number of separate experiments required to reach statistical significance for a given increase of DNA elution rate.

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The effect of treatment with indomethacin on methylazoxymethanol-induced rat large bowel carcinomas was investigated. Eight-week-old male Donryu rats received an intraperitoneal injection of 20mg/kg body weight of methylazoxymethanol acetate once a week for 6 weeks. Fifteen rats were sacrificed at the 25th week. It was confirmed that the incidence of large bowel tumors (adenocarcinomas) was 60% and the mean number of tumors per tumor-bearing rat was 2.0. The other rats (23∼30 rats in each group) were given the treatment with an intrarectal instillation of 7.5mg/kg body weight of indomethacin, 7.5mg/kg of hydrocortisone, 75mg/kg of PS-K, vehicle alone, or non-treatment daily from the 27th to 29th week. All of these rats were sacrificed at the 30th week. The tumor incidence was 50% or 55% in indomethacin- or hydrocortisone-treated rats. It was significantly lower than 83% or 87% of the rats treated with PS-K or vehicle, or untreated. The mean number of tumors was also smaller in those 2 groups of rats (2.0 or 2.1 tumors) than in these 3 groups (3.5 or 3.3 tumors). The results demonstrated that the intrarectal dose of indomethacin and hydrocortisone inhibited the development of tumors from microscopic carcinoma lesions in the large bowel and growing further. It seems that indomethacin might be effective to treat the early stage disease with relatively small number of growing tumor cells.

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This study was undertaken to evaluate the carcinogenic effect of benzidine on the urinary bladder of mice, and the effect of DL-tryptophan on the induction of bladder cancer.
Benzidine plus DL-tryptophan or benzidine alone mixed with a commercial basal diet was fed to groups of ICR strain female mice for 20 weeks, after a glass bead had been inserted into the bladder. Control mice were fed the basal diet throughout the experimental period. All the surviving mice were killed 63 weeks after start of the study.
Benzidine administered with or without DL-tryptophan did not induce tumors of the urinary bladder in these mice. Hepatomas developed in 34 of 41 mice (82.9%) fed benzidine and in 24 of 51 mice (47.1 %) fed benzidine with tryptophan. DL-Tryptophan counteracted the effect of benzidine and significantly reduced the development of hepatomas.

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