Manifestation of a chemotherapeutic effect of Vincristine and alkylating agents on rat leukemia, DBLA-6, differed according to the route of tumor inoculation or drug administration. The leukemic cells infiltrated into bone marrow far more predominantly by intravenous inoculation than by intraperitoneal inoculation. On the other hand, the distribution of Vincristine into bone marrow was markedly higher by intravenous injection than by intraperitoneal injection, while the distribution of alkylating agent, 3, 3'-dimesyloxydipropylamine hydrochloride (No. 864), was rather low either by intravenous or intraperitoneal injection. These results seemed to suggest that a relationship between tumor localization and drug distribution was a definitive factor in the manifestation of chemotherapeutic effect of agents in screening procedures.

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The simultaneous administration of bis(3-methylsulfonyloxypropyl)amine p-toluenesulfonate (designated as 864-T) with 6-mercaptopurine or cytosine arabinoside exhibited a marked synergistic action with two experimental systems, the subcutaneous solid tumor of Yoshida sarcoma in Donryu rats and the ascitic L-1210 in BDF₁ mice. The combination of 864-T with nitrogen mustard N-oxide, cyclophosphamide, Mitomycin-C, and prednisolone or Chromomycin also showed a tendency to enhance the effect of 864-T, but combination with 5-fluorouracil did not show any enhancement in both experimental systems, but rather unfavorable effect on treatment with 864-T.

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The experimental lymph node metastasis was induced in the ipsilateral lumbar node following the inoculation of ascites hepatoma cells into the muscle of a hind leg of Donryu rats. At various time intervals after the inoculation, the rats were used to examine the distribution of ⁵¹Cr-labeled lymphoid cells which had been prepared from the lymph nodes of normal rats and injected intravenously one day beforehand. Histological examinations of the removed lymph nodes were performed by the usual technique with Hematoxylin and Eosin stain. The distribution of ⁵¹Cr-labeled lymphiod cells was found to increase transiently in the lumbar node draining the tumor inoculated. It was kept at a certain level in the node involved slightly with metastasized tumor cells even when the interval after the inoculation became longer, but it decreased very markedly in those damaged extensively. In addition, the degree of sinus histiocytosis in the node seemed to be related significantly to the distribution of ⁵¹Cr-labeled lymphoid cells.
These results were discussed with regard to the host immune reaction in the node draining the tumor.

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Isoenzymes of lactate (LDH), malate (MDH), and glucose-6-phosphate (G6PDH) dehydrogenases have been detected in experimentally induced salivary gland tumors. Total LDH activity generally increased in the tumors and the LDH zymograms showed a skeletal muscle type. An unknown extra band, in more faster position than LDH₁ was detected in a few tumors. Total activity and isoenzymic migration of MDH showed no remarkable changes during malignant transformation. In some tumors, a unique band which migrated more anodal than supernatant MDH appeared. G6PDH isoenzymes were resolved into three components. The total stainabilities were elevated in tumors compared with normal tissues. Various patterns were presented according to the stainability of each component.

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Localization of in vivo liver catalase-depressing substance in rats was studied.
1) Nuclei were isolated from Rhodamine sarcoma and from four different organs of normal rats; brain, spleen, kidney, and liver. When these nuclei were injected into mice, the catalase activities of the livers decreased in the order of "Rhodamine sarcoma" "brain" "spleen" "kidney" "liver." The homogenates of Rhodamine sarcoma and brain hardly showed catalase activity, whereas that of spleen and kidney showed approximately 10% and 40%, respectively, of the catalase activity of that of liver.
2) Chromatin was prepared from Rhodamine sarcoma and then fractionated into the three major components; histone, non-histone protein, and DNA. When these fractions were injected into mice, the catalase activities of the livers decreased with the histone and the non-histone protein but not with the DNA. At small doses, the extent of the decrease with the non-histone protein was significantly higher than that with the histone. Poly-L-lysine, a synthetic poly-cation, when injected into mice, also decreased the catalase activities of the livers to almost the same extent as the histone. By isoelectric fractionation, the non-histone protein was further divided into two fractions; one of pI<4 and the other of pI 4-7. When these two fractions were injected into mice, the pI 4-7 fraction decreased the catalase activities of the livers significantly at small doses, but not the pI<4 fraction.
3) These findings indicate that two different kinds of in vivo liver catalase-depressing substance are present in the chromatin; one is histone and the other a non-histone protein. Probably, the former is not different in kind and amount for all the organs, and lower the catalase activity of a cell, the higher is the content of in vivo liver catalase-depressing non-histone protein.

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Rat mammary tumors induced with two carcinogens, N-nitrosobutylurea (NBU) and 7, 12-dimethylbenz[a]anthrancene (DMBA), were comparatively studied from the viewpoint of hormone responsiveness.
First, ovariectomy of autochthonous rats resulted in marked reduction of tumor size within 3 weeks. Most of DMBA-induced mammary tumor disappeared completely thereafter, while half of NBU-induced mammary tumor survived and kept growing. Restoration of mammary tumor growth in ovariectomized rats was attained by grafting the intact ovary in accord with the 2-fold increase of serum mammotropin level as revealed by the radioimmunoassay.
Second, all NBU-induced mammary tumors (8 cases) became palpable as early as 3 weeks after tumor transplantation in syngeneic female rats. On the other hand, 4 of 10 cases of DMBA-induced mammary tumors did not take and the tumor growth rate of the rest was much slower than that of the NBU-induced mammary tumor.
Third, ovariectomized, intact, or castrated male Wistar/Furth rats accepted the NBU-induced mammary tumor grafts but not the DMBA-induced mammary tumors. Only in exceptional cases, there occurred a successful take of a DMBA-induced mammary tumor in a male co-grafted with a mammotropic pituitary tumor.
An attempt to correlate the growth characteristics of the mammary tumor and the histological appearance gave inconclusive result.

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Attempts were made to investigate the occurrence and topography of surface antigen on the cells of mouse Friend virus-infected tumor in rats by the indirect immunoferritin method. FV-KMT-17 was used for Friend virus-infected rat tumor which was obtained by artificially infecting the KMT-17, a methylcholanthrene-induced transplantable tumor in rats, with Friend virus. Antigens investigated were histocompatibility antigen of rats (R^w) and tumor-specific surface antigen (TSSA) on the cells of FV-KMT-17 and KMT-17, as well as virus-induced specific antigen (VSSA) and virus antigen on FV-KMT-17 cells.
R^w and TSSA were present on FV-KMT-17 and KMT-17 cell surface in similar pattern of ferritin labelings. VSSA and virus antigen were also found on FV-KMT-17 cells. R^w, TSSA, and VSSA, however, were absent on Friend virus morphologically identified as type-C virus particles which were produced from FV-KMT-17 cells. Significance of these results is discussed briefly with reference to xenogenizaton of tumor which is defined as immunological regression of tumor by artificially infecting the tumor cells with virus.

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Antitumor and immunosuppressive activities of some lankacidin group (T2636) antibiotics were investigated in vivo and in vitro. Lankacidin-C, Lankacidin-C 8-propionate, and Lankacidin-C 14-propionate, given intraperitoneally, showed inhibitory effects at doses ranging from 25 to 1, 000mg/kg on the growth of the following tumors; leukemia L-1210, lymphosarcoma 6C3HED/OG sensitive to l-asparaginase, and melanoma B-16 in mice. Leukemia L-1210 cells resistant to 6-mercaptopurine or to cytosine arabinoside were also sensitive to the antibiotics. Lankacidin-C 8-propionate and Lankacidin-C 14-propionate inhibited the proliferation of HeLa cells in concentrations of more than 50μg/ml in vitro, whereas Lankacidin-C was not inhibitory.
Lankacidin-C at high doses suppressed the production of antibody against sheep erythrocytes in mice when administered before or after antigenic stimulation. On the contrary, Lankacidin-C 8-propionate slightly suppressed the anibody production only after antigenic stimulation, and Lankacidin-C 14-propionate had no suppressive activity in any conditions.

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Fourteen out of 24 (58%) mice which received combined treatment with a short-term oral administration of N-nitrosobutylurea (NBU) and subcutaneous injection of azathioprine (Imuran), developed either thymic lymphomas or reticulum cell neoplasm with the mean latent period of 189 days. The thymic lymphomas thus induced possessed the Gross-specific cell-surface antigen in cytotoxicity test. Cell-free transmission of these thymic lymphomas in W/Fu rats failed to confirm the implication of viral agent. No leukemia occurred in mice treated with a short-term administration of NBU alone. Eleven out of 38 (29%) mice, which were treated with Imuran alone developed leukemia with a latency of 182 to 377 days. The immunological implication in induction of leukemia is discussed.

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The rate of cell loss of mouse mammary carcinoma cells during tumor growth was estimated with ¹²⁵IUdR. The rate was 0.008 per hour for the small tumor, and 0.004 per hour for the large tumor.

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The in vivo chemotherapy with several anticancer agents was investigated for their effect on the in vitro lymphocyte blastoid transformation in cancer patients and animals. 5-Fluorouracil and Bleomycin showed no suppressive effect. Mitomycin-C showed a slight effect, and cyclophosphamide showed a strong suppressive effect.

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Among α-, β-, and γ-isomers of benzene hexachloride, both α- and γ-isomers induced a typical hepatoma, and none was found in mice fed the β-isomer. Hepatoma more often developed in male than in female mice. α-Fetoprotein was not detected in the serum of animals with hepatoma, by the Ouchterlony method.

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Type-C virus particles, morphologically similar to the murine leukemia viruses, were found in two cell lines derived from normal and tumor cells of rats. Virus particles were recovered effectively by in vitro cell culture and treatment of cells with BUdR.

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Antitumor activity of esters and halogeno derivatives of cyclocytidine and cytidine arabinoside was examined in L-1210 system. Esterification decreased the antitumor activity of the mother compounds. Substitution with halogen at 5-position increased the toxicity of cyclocytidine and decreased the antitumor activity of cytidine arabinoside.

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Antitumor activity of constituents and products of Ps. aeruginosa was examined. ED₅₀ of the protein moiety of endotoxin for antitumor activity against ascites sarcoma-180 was about 1μg/kg/day, whereas that of other constituents and products tested was over 100μg/kg/day.

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The carcinogenicity of Petasites japonicus, a kind of coltsfoot, was studied in inbred strain ACI rats. Experimental groups received the 4 or 8% coltsfoot diet. They developed hemangioendothelial sarcoma of the liver, liver cell adenoma, and hepatocellular carcinoma. These tumors were not observed in any of the control rats.

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This paper describes the experiment in which the inhibitory effect of Candida utilis mannan preparation (Cetavlon pH 10-precipitate of the original hot-water extract) was demonstrated for the first time in the system of a primary tumor, 3-methylcholanthrene-induced epithelial tumor in mice.

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An increase in hepatocellular mitosis in mice bearing ascitic Ehrlich tumours reaches a peak 6 days after transplantation, but no increased mitotic activity is detectable 12 and 16 days after transplantation. Mice bearing 10-19-day-old subcutaneous Ehrlich tumour transplants all show increased hepatocellular mitosis.

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