著者
永田 親義 今村 詮 福井 謙一 斉藤 肇
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.54, no.4, pp.401-414, 1963-12-31 (Released:2008-10-23)
参考文献数
23

Results of the quantum biological study of an interaction of potent carcinogens such as 4-nitroquinoline 1-oxides and aromatic hydrocarbons with tissue components, especially with deoxyribonucleic acid (DNA), are presented and chemical carcinogenesis is discussed in connection with charge transfer phenomenon. An equation is derived to obtain the charge transfer quantity between two constituent molecules in the charge transfer complex, and distinct parallelism is found between the quantity of charge transfer and carcinogenic activity. From this result, it is suggested that the quantity of charge transfer is more important in the genesis of tumor than the charge transfer force. Summation of an alteration of base paring in Watson-Crick stereo-model of DNA resulting from the charge transfer between DNA and the carcinogens is deemed to be the cause of tumor.
著者
永田 親義 今村 詮 斉藤 肇 福井 謙一
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.54, no.1, pp.109-117, 1963-03-31 (Released:2008-10-23)
参考文献数
23

The changes of π-electron distribution in atoms in purine bases participating in the hydrogen-bond formation in Watson-Crick model of deoxyribonucleic acid are calculated by the simple linear combination of atomic orbital-molecular orbital (LC-AO-MO) method assuming that the alkylating agents attack the guanine at its 7-N position and adenine at its 7-N and 3-N positions. The changes in electron density are believed to make an alteration of the hydrogen bond with respect to the mode of pairing. It is assumed that the tautomeric change of guanine-cytosine pair results and weakens the hydrogen bond strength of adenine-thymine pair. These changes are discussed in relation to the biological effect of alkylating agents such as mutagenic, carcinogenic, and carcinostatic activities.
著者
小林 博 宮下 孝 武田 勝男
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.58, no.1, pp.101-104, 1967-02-28 (Released:2008-10-23)
参考文献数
8

The cause of recent increase in lung cancer mortality in Japan may possibly be attributed to "pseudo-increase" by the improvement in diagnosis and discovery besides the "true rise". It is surmised that approximately 30% (or over?) may be due to this "pseudo-increase".
著者
寺山 宏 折井 弘武
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.54, no.4, pp.455-464_1, 1963-12-31 (Released:2008-10-23)
参考文献数
8

Following previous experiments on the dye-protein binding in in vitro system, the dye-protein binding in in vivo systems is reported, in which 4-dimethylaminoazobenzene amine-N-oxide was administered intragastrically or intramuscularly to rats, mice, and guinea pigs. The binding took place at the site of injection as well as in the liver in the case of intramuscular administration. Amount of the protein-bound dye increased with the dose. LD50 values of 4-dimethylaminoazobenzene amine-N-oxide were compared with that of 4-dimethylaminoazobenzene, using rats and mice, both by intragastric and intraperitoneal administration. The highest toxicity was observed in the intraperitoneal injection of 4-dimethylaminoazobenzene amine-N-oxide. The toxicity decreased to 1/5 (mice) and to 1/15 (rats) in the case of intragastric injection. Addition of 4-dimethylaminoazobenzene amine-N-oxide in the drinking water (0.03%) to rats and mice caused malignant hepatomas in rats, but only adenomatous growth in mouse liver.
著者
林清 五郎 植木 寛 植木 洋子
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.54, no.4, pp.381-390, 1963-12-31 (Released:2008-10-23)
参考文献数
14

The antitumor activities of 4, 5-bis(ethyleneimino)-1, 2-benzoquinone (OBE), 2, 5-bis(ethyleneimino)-1, 4-benzoquinone (PBE), and 4-ethyleneimino-1, 2-naphthoquinone (NQE) were investigated in Ehrlich carcinoma. OBE was effective not only in prolonging the life-span of mice bearing Ehrlich ascites carcinoma but also in retarding the growth of the solid form of the same tumor. This compound was proved to be effective even in a smaller dose than the minimum effective dose of PBE, with lower toxicity than the latter. With NQE, the mice bearing the same ascites tumor did not survive longer than the control.Ratio of the number of neutrophils to lymphocytes (N/L) in the peripheral blood was compared with the non-treated and the treated groups of animal bearing the tumor. Generally speaking, the more progressed the growth of the ascites tumor was, the greater the value of N/L, but such increase of N/L was eventually observed in case of leucopenia induced by these agents. It may therefore be said that the observation of change of N/L should be considered as an element for evaluation of the result of screening experiment.
著者
遠藤 英也 久米 文弘
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.54, no.4, pp.443-453, 1963-12-31 (Released:2008-10-23)
参考文献数
23
被引用文献数
2

From the fact that 4-hydroxyaminoquinoline 1-oxide (4-HAQO) as well as 4-nitroquinoline 1-oxide (4-NQO) have λ-phage inducing ability in lysogenic Escherichia coli K12 and from the studies of Okabayashi, showing that not only 4-NQO but also 4-HAQO are mutagenic and able to produce the phenotypically same mutants in Aspergillus niger, similarity between these two substances in their biological actions was examined on (1) carcinogenicity, (2) growth-inhibiting action, and (3) intranuclear inclusion-forming action.1) 4-HAQO•HCl in peanut oil and cholesterol mixture was injected into the subcutaneous tissue of rats. Subcutaneous tumors were induced in 8 of the 15 effective rats (53%) in the first group and in 16 of 17 rats (94%) in the second group.2) Three groups, consisting of 10 mice each, were inoculated with Ehrlich ascites tumor cells intraperitoneally. Twenty-four hours after the inoculation, the first group was treated daily with 0.5mg/kg body weight of 4-HAQO•HCl dissolved in physiological saline containing 0.4% carboxymethylcellulose, the second group with 7mg of 4-NQO, and the third with solvent alone. The treatment was continued for 10 days. All the mice of the first group and all but 2 mice of the second survived over 50 days, whereas the third (control) group survived only 15 days.3) When the Chang's liver cells were incubated for 24 hours at 37° in a culture media containing 4-HAQO•HCl in the final concentration of 7×10-5M, intranuclear inclusions phenotypically identical with those induced by 4-NQO were produced in about 60% of all the cells.These results were discussed in relation to the carcinogenic mechanism of 4-NQO.
著者
平木 潔 入野 昭三 三好 勇夫
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.54, no.4, pp.427-432, 1963-12-31 (Released:2008-10-23)
参考文献数
13

Five of eight inbred Swiss mice given repeated injections of a small amount of benzene in olive oil developed subcutaneous sarcomas. One of the three tumors transplanted grew and is now maintained as transplants. Morphology of these tumors and histological changes in other organs are described. The present results indicate that benzene is capable of inducing solid malignant tumors in mice. No leukemia or lymphoma was observed among these experimental mice.
著者
森 和雄
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.54, no.4, pp.415-425_3, 1963-12-31 (Released:2008-10-23)
参考文献数
17

Cancers of the lung were induced by the repeated subcutaneous injections of 4-nitroquinoline 1-oxide in three groups of rats receiving a total amount of 15, 11, and 7.25mg, respectively. The lung cancer was found in 16 (37.2%) out of 43 effective rats that survived more than 223 days. These cancers were usually adenocarcinomas (30.2%), but there were also some epidermoid carcinomas (7.0%). Both adenocarcinoma and epidermoid carcinoma gave rise to metastases in distant organs. Almost all the rats had multicentric pulmonary adenomas. Various degrees of hyperplasia and metaplasia of bronchial epithelia or alveoli were also observed. Subcutaneous sarcomas often arose in the area of application of the carcinogen. A transplantable strain of the epidermoid carcinoma was separated successfully.
著者
岡村 裕 藤井 節郎 河内 卓 川波 寿 桑野 信彦 山村 雄一
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.53, no.4, pp.365-370, 1962 (Released:2008-10-23)
参考文献数
18
被引用文献数
1

A basic protein fraction having toxohormone activities, isolated from rat Rhodamine sarcoma, was subjected to enzymatic hydrolysis with trypsin, pepsin, and pronase, resulting in the splitting of 12.3%, 19.1%, and 57.4% of peptide bonds of the basic protein respectively.The effect of the hydrolysis on the toxohormone activities of the basic protein was determined by bioassay with rats or mice. Liver catalase depression was markedly diminished by hydrolysis with pronase and pepsin but not by trypsin. Plasma iron decrease was affected by none of these enzymes. Liver tryptophan pyrrolase depression was markedly diminished by hydrolysis with any one of these enzymes.These results suggest that these three different activities of toxohormone are associated with different chemical entities of the basic protein.
著者
KENICHI FUKUI AKIRA IMAMURA CHIKAYOSHI NAGATA
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.51, no.2, pp.119-123, 1960-06-30 (Released:2008-10-23)
参考文献数
20
被引用文献数
1

The electronic structure of 4-nitroquinoline N-oxide and related compounds were investigated. The frontier electron density and the approximate superdelocalizability for nucleophilic reaction at the carbon atom to which nitro group is attached had a definite correlation with the carcinogenic activity. This is a support for our proposition that the interaction with the nucleophilic center in the body might be primarily concerned with the production of cancer by all types of chemical carcinogens.
著者
吉田 光二 星 昭夫 榑谷 和男 金井 貞 市野 元信
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.66, no.5, pp.561-564, 1975-10-31 (Released:2008-10-23)
参考文献数
12

Effect of substitution of 5-position of cyclocytidine with fluorine on its antitumor activity in cultured cells was examined. 5-Fluorocyclocytidine was active against cultured L-5178Y cells similar to cyclocytidine. IC50 of the compound was 0.054μg/ml. This compound inhibited thymidine incorporation into acid-insoluble fraction of the cells. Cell growth inhibition by 5-fluorocyclocytidine was reversed by deoxycytidine but not by thymidine and deoxyuridine. On the other hand, cell growth inhibition by 5-fluorouracil was reversed by thymidine and deoxyuridine. As a result, site of action of 5-fluorocyclocytidine was considered to be similar to that of cyclocytidine and not to 5-fluorouracil.
著者
星 昭夫 官沢 文彦 飯郷 正明 榑谷 和男
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.66, no.5, pp.539-546, 1975-10-31 (Released:2008-10-23)
参考文献数
12
被引用文献数
2

Combination effect of antitumor agents, including cyclocytidine and cytosine arabinoside, was evaluated on the conception of pharmacological synergism and not of therapeutic synergism. Ascites sarcoma-180 and L-1210 leukemia were used as tumor systems. In sarcoma-180 system, combinations of cyclophosphamide plus cyclocytidine or cytosine arabinoside by simultaneous administration and cyclocytidine plus Daunorubicin or Vinblastine by alternate administration provided synergism. In L-1210 system, many compounds in combination with cyclocytidine or cytosine arabinoside in both simultaneous and alternate administrations provided synergism. Combination effect of agents was affected by the schedule of drug administration. It was found that the combination effect of drugs in one tumor system cannot be generalized to that in other tumor systems, even though equally effective doses of agents were administered in both tumor systems. Toxicity of cytosine arabinoside in combination with other drugs was affected by the schedule of administration. Compounds which provided synergism in simultaneous administration provided antagonism in alternate one. As a result, it was found that alternate administration of drugs is advantageous for the activity and diminution of toxicity to the host animal.
著者
平山 八彦 杉原 太助 浜田 福三郎 金井 貞 疋田 重太郎 荒木 靖雄 博谷 和男 星 昭夫
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.65, no.2, pp.153-161, 1974-04-30 (Released:2008-10-23)
参考文献数
23

The distribution in tissues and excretion of cyclocytidine (2, 2'-anhydro-1-β-D-arabinofuranosylcytosine hydrochloride) and its metabolites in urine and feces of macaca monkeys (Macaca irus, Macaca fuscata, and Macaca mulata) and in beagle dogs were examined by the spectrophotometric assay. Distribution of cyclocytidine in plasma and tissues of rats was also examined.The administered cyclocytidine showed a half-life of 22min in plasma of dogs and monkeys, whereas the half-life of aracytidine (1-β-D-arabinofuranosylcytosine hydrochloride) was 47min in plasma of dogs and less than 5min in plasma of monkeys, because of rapid deamination of the comvound to arauridine (1-β-D-arabinofuranosyluracil) in the latter species. Cyclocytidine exhibited maximum concentration in tissues of rats and monkeys at 20 to 40min after the administration, but its metabolites, aracytidine and arauridine, were not detected in these tissues. Cyclocytidine levels in tissues diminished thereafter but were detected within the next 40 to 80min, Neither cyclocytidine nor its metabolites could be detected in the brain. When cyclocytidine was administered intravenously in dogs and monkeys, 65-85% of it was excreted in urine, almost all as intact cyclocytidine, and small amounts of aracytidine and arauridine were detected. On the other hand, the administered aracytidine was excreted only as arauridine in urine of monkeys, and aracytidine and arauridine in dogs. Cyclocytidine and its metabolites were not detected in feces of both species.It might be suggested that the distribution and elimination rate of cyclocytidine after its intravenous administration is not affected by the presence of cytidine deaminase in plasma and tissues.
著者
星 昭夫 官沢 文彦 榑谷 和男
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.63, no.3, pp.353-360, 1972-06-30 (Released:2008-10-23)
参考文献数
12
被引用文献数
4

The antitumor activity of cyclocytidine was examined in a variety of tumors. Cyclocytidine was active against adenocarcinoma-755, Nakahara-Fukuoka sarcoma, ascites sarcoma-180, Ehrlich ascites carcinoma, L-1210 leukemia, and C-1498 leukemia. Cures (60-day survivors) were observed at 500mg/kg/day×5 or more of the compound in the L-1210 system and therapeutic ratio was as high as 50, though that of other known antitumor agents tested, including 1-β-D-arabinofuranosylcytosine (Ara-c), was less than 12. Therapeutic index of cyclocytidine in the solid and ascites tumors was always greater than that of Ara-c. Cumulative toxicity of cyclocytidine was surprisingly low and LD10 was 790mg/kg/day×5, whereas that of Ara-c was 82mg/kg/day×5. Cyclocytidine appears therefore to have advantages over Ara-c for clinical use.
著者
星 昭夫 官沢 文彦 榑谷 和男 実吉 峯郎 新井 祥子
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.62, no.2, pp.145-146, 1971-04-30 (Released:2008-10-23)
参考文献数
8
被引用文献数
4

2, 2'-O-Cyclocytidine was active against L-1210 leukemia. Cures were observed at the optimal dose of the compound, though no cures were obtained at any dose of any of the known antitumor agents. The compound was less toxic than 1-β-D-arabinofuranosyl-cytosine and resistant to cytidine deaminase.
著者
福岡 文子 徳善 玲子 星 昭夫 江上 不二夫 長沢 金蔵 加藤 好雄
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.60, no.2, pp.187-197, 1969-04-30 (Released:2008-10-23)
参考文献数
21

Derivatives of 2-acylamido-6-purinethiol and/or 2-acylamido-9-alkyl-6-purinethiol were synthesized and the 2-acylamide derivatives were compared with the parent compound as to their antitumor activity and toxicity. The antitumor activity was assayed mostly with NF-sarcoma, which is known to be highly sensitive to this class of nucleic acid base analogs, but also using other types of tumors.Among the 2-acylamide derivatives, formamide and especially isobutyroylamide derivatives were found to be the most active, but not markedly more active than the parent compound. A slight decrease in the toxicity was noted among the derivatives with high antitumor activity.
著者
官沢 文彦 星 昭夫 榑谷 和男
出版者
The Japanese Cancer Association
雑誌
GANN Japanese Journal of Cancer Research (ISSN:0016450X)
巻号頁・発行日
vol.65, no.1, pp.55-60, 1974-02-28 (Released:2008-10-23)
参考文献数
22
被引用文献数
3

Interaction of antitumor agents in activity and in toxicity was examined separately. Ascites sarcoma-180 and ddN mice were used as the tumor system.Interaction was evaluated on the concept of pharmacological synergism and not of therapeutic synergism. In activity, 18 out of 91 combinations provided synergism and most of them contained alkylating agents and antibiotics. Antitumor agents were therefore classified into two groups from the point of drug interaction. Synergism was observed in combinations of agents in Group I, alkylating agents, antibiotics, and alkaloids. In combination of agents in Group II (antimetabolites and others), additive action was observed. As a result, 18, 65, and 8 combinations provided synergism, additive action, and antagonism, respectively.On the other hand, in toxicity, 13, 27, and 38 out of 78 combinations provided synergism, additive action, and antagonism, respectively. The combination that provided synergism in activity and antagonism in toxicity were 8 out of 91 combinations tested. In general, fortunately, combinations of antitumor agents were more than additive in activity and less than additive in toxicity.