Attempts were made to prevent methylcholanthrene tumorigenesis in mice by immunization with the insoluble lipoprotein of methylcholanthrene-induced sarcomas of the same strain of mice. Swiss/Mk mice were intensively immunized with the insoluble lipoprotein fraction extracted by the Thomas method or with the supernatant fraction of isogenic methylcholanthrene-induced tumor cells, or normal cells with Freund adjuvant. As control groups, mice pretreated with Freund adjuvant alone and untreated mice were prepared. Each mouse was injected with 0.5mg of 3-methylcholanthrene as a pellet or an olive oil suspension. Several series of repeated experiments always revealed the inhibitory effect of immunization with the insoluble lipoprotein fraction of a tumor on tumor occurrence. The tumor supernatant showed a slight inhibitory effect but was not so marked as the insoluble lipoprotein fraction. Tumor occurrence in groups immunized with normal insoluble lipoprotein or normal supernatant and that of adjuvant injection showed no significant difference from that in untreated group. Neither histological nor biological differences have been found among the developing tumors in the experimental groups.

View full abstract

The treatment of animals with non-neoplastic or neoplastic tissue before or after tumor transplantation inhibited the growth of transplanted tumor cells. This phenomenon was most clearly demonstrated when a sub-effective dose of chemotherapeutic agent was administered. In animals bearing a spontaneous tumor, the growth of auto-transplanted tumor was inhibited as compared with that of the same tumor transplanted in isologous animals. These findings suggested that the acquired resistance of the host against tumor inhibits the growth of a newly transplanted tumor.

View full abstract

The three slow-growing variant sublines of Yoshida sarcoma, LY-7, LY-5, and LY-336, as compared with the parent tumor, showed a marked increase in activity to synthesize glycogen from added glucose in vitro. The activity increases roughly parallel with the increasing survival time of the tumors.
The glyconeogenetic activity of Yoshida sarcoma, as determined by the incorporation of pyruvate-carbon into glycogen, was enhanced on the addition of glucose and depressed by the presence of an inorganic phosphate. Under the conditions employed, LY-336, the slowest-growing tumor, showed a greater glyconeogenetic activity than any of the other three tumors. No significant difference was observed in the glycolytic and glucose-oxidizing activities of the four strains of the tumor.
The possible significance of these findings is discussed in relation to the biological characteristics of these variant-sublines.

View full abstract

Further detailed observation has been made on the ultrastructure of the six strains of Yoshida ascites hepatoma representing various growth rates and pathological characteristics. Common to all the ascites hepatoma were the large, irregular nuclei with hypertrophied nucleoli, increased free ribosomes, and no microbodies.
The present investigation throughout many transplant generations has revealed several genetically defined characteristics for each strain. These fine cytological characteristics are as follows: AH-13-clumped and dispersed glycogen granules, fine fibrils, and sparse endoplasmic reticulum; AH-130-well-developed Golgi lamellae, fine fibrils, single cisternae of endoplasmic reticulum, and short tight junction; AH-130R-mitochondria with electron-lucent matrix; AH-272-mitochondria with electron-lucent matrix, fine fibrils, and single cisternae of endoplasmic reticulum; AH-601-small, round or oval mitochondria, relatively increased number of dilated cisternae of rough-surfaced endoplasmic reticulum, short tight junction, and increased site of intermediate junction; AH-7974-small and compact mitochondria, elongated cisternae of rough-surfaced endoplasmic reticulum, occasionally forming parallel array, typical junctional complex-tight, intermediate, and macula adhaerens (desmosome) which is described in detail in this paper, and vesicles containing dense amorphous materials along the intercellular canaliculi.
The fine cytological characteristics of each strain were discussed with their pathological properties.

View full abstract

A long-term tissue culture cell line was established from the Friend virus ascites sarcoma. The cultured cells grew free in petri dishes showing the same morphology as in vivo and were easily transplantable into ddOM mice. Cultivation from a single cell resulted positive in about one-half of the trials with feeder layer. Both bioassay and electron microscopic examination of the cultured cells revealed virus production in the same degree as in vivo. Metamorphosis of tumor cells into fibroblast-like cells, frequently encountered both in vitro and in vivo, may suggest their innate potency to differentiate along fibroblastic line. Successful cultivation of the deficient virusproducing subline of this tumor may be useful for further analysis of induction phenomenon of infectious virus by ionizing radiation of such cells.

View full abstract

Adenovirus type 12 was inoculated intraperitoneally into newborn hamsters. At selected periods, the soft peritoneal tissues were excised and transplanted subcutaneously into 16- to 29-day-old hamsters. With the tissues taken at 6 hours or more after the virus inoculation, tumors developed at the transplanted site. The period from virus inoculation to excision and transplantation of the soft peritoneal tissues, and from transplantation to development of grossly recognizable tumors ranged from 24 to 38 days, which correspond to the average latent period for tumor development in hamsters intraperitoneally inoculated with the virus at birth. The virus was not isolated from the soft peritoneal tissues similarly excised from hamsters inoculated with the virus at birth. None of 10 young adult hamsters injected with the virus developed any visible tumors during 46 to 367 days of observation.
These results would imply that (1) the tumors developed at the site of tissue transplantation originate from the cells in the transplanted tissues, which would have been already neoplastically transformed or destined by the virus; and (2) transformation or transition of the target cells to malignant cells will be completed in 6 hours after the virus inoculation.

View full abstract

1) Induction of ovarian tumor with a single intragastric instillation of a large but tolerable doses of 7, 12-dimethylbenz[a]anthracene (DMBA) was investigated on young female mice of C3H and C57BL strains, rats of Sprague-Dawley strain, guinea pigs, and rabbits. The ovarian tumor occurred in a high incidence only in C3H mice.
2) The induction of ovarian tumor in C3H mice with DMBA by various routes of administration such as intragastric instillation, intraperitoneal or intravenous injection was studied. The following tumor incidences were obtained in the treated mice: Single feeding, 59% until 7th month; intraperitoneal injection, 36% until 4th month; single intravenous injection, variable percentages at each month and average 57% after 6 months. Intraperitoneal injection of DMBA induced ovarian tumor earlier and in higher incidence than by other two routes but mortality of mice was unfortunately very high.
3) Histological observations revealed no normal ovaries in C3H mice given DMBA intravenously. Follicular structures were destroyed and oocytes vanished within one month. Proliferation of granulosa cell following its earlier non-specific pathological change progressed from microscopical nodule to a sizable gross tumor. These tumors were all granulosa-celled type.
4) Granulosa cell tumor arose probably from surviving granulosa cells in the partially degenerated follicles and its growth was stimulated by pituitary gland but there was still a probability that granulosa cell tumor might have originated from theca cells.
5) Frequent study of vaginal smears demonstrated possible association between the presence of tumor and estrogen activity.

View full abstract

To study the influence of activation of metabolic function of carcinogen to chemical carcinogenesis, effect of barbital, an inducer of enzymes related to drug metabolism, was studied on the development of liver cancer in the rat fed with 4-dimethylaminoazobenzene (DAB), and compared with that of 3-methylcholanthrene, known to antagonize the carcinogenic effect of DAB. In an animal experiment of a long period, the incidence of cancer development was much lower in barbital group than that in 3-methylcholanthrene group. Comparative studies were also made on the quantitative measurement of DAB metabolites in urine and bile, and on the activities of some enzymes in the liver of rats fed with DAB plus barbital diet, DAB diet, or basic diet alone. Excretion of DAB metabolites, especially azo dye glucuronides, in the bile increased in the middle stage of the barbital feeding.

View full abstract

Twenty-eight cases of primary lung cancer were studied by electron microscopy in detecting ultrastructural differences between cancer cells and non-malignant cells of human lungs.
In a lung cancer tissue, three kinds of cancer cells are observed; dark cells, light cells, and goblet cell-like cells (presently designated as mucous cells). The latter cells are commonly observed in adenocarcinoma and uncornified epidermoid carcinoma of peripheral origin, but rarely in cornified epidermoid carcinoma and undifferentiated carcinoma of central origin.
The cancer cell nucleus is variable in size, shape, and structure. The chromatin clumps of cancer cells are irregularly distributed throughout the nuclei and their size and shape are very variable, unlike those of non-malignant cells. Undifferentiated carcinoma cells (small cell type) are often strikingly characterized by many tiny nucleoli while they reveal a marked condensation of chromatin clumps.
Many abnormal findings are observed suggesting an incomplete maturation or differentiation of cancer cells, i.e., incomplete polarity, long microvilli or striated borders instead of cilia, extraordinarily developed Golgi apparatus or endoplasmic reticulum, etc. Desmosomeas nd tonofibrils are abundant in cornified epidermoid carcinoma, a few in uncornified epidermoid carcinoma and adenocarcinoma, and none in undifferentiated carcinoma. On ultrastructure, it is impossible to differentiate uncornified epidermoid carcinoma from adenocarcinoma of the lung periphery.

View full abstract

Spontaneous mammary tumour incidence, at death, of intact C3H(Jax) virgin female mice was not altered by treatment with testosterone propionate, given upto the beginning of tumour age. In 6 out of 12 mice, testosterone delayed the appearance of tumours and thus added to their longevity significantly. The type of mammary tumours obtained in testosterone-treated female mice was largely similar to the spontaneous and unlike the chemically induced ones.
The yield of ovarian tumours induced by 7, 12-dimethylbenz[a]anthracene (DMBA) was significantly greater in C3H(Jax) mammectomised mice when treated with testosterone. It is suggested that testosterone has a promoting action for chemically induced ovarian tumours in mice. Subcutaneous fibrosarcomas were induced in DMBA-treated mammectomised C3H(Jax) female mice given testosterone. They were not obtained in comparable groups treated with testosterone alone or with DMBA alone. This observation supports the suggestion that testosterone has a promoting rôle in the mechanism of chemical carcinogenesis.

View full abstract

A microspectrophotometric evaluation of the DNA content of tumor cell nuclei was undertaken in 24 cases of fibroadenomas and 30 cases of carcinomas of the human breast. There was a general trend that fibroadenomas of the breast showed the DNA values lying in a diploid range, with limited deviation among the cells, while in carcinomas of the breast, the DNA values were slightly or definitely higher than the basic diploid value with a larger scatter from cell to cell. The modal DNA value from malignant tumors was distributed from hypodiploid to hypotetraploid ranges. Further, there was no direct correlation between the DNA content and the histopathological pattern of the tumor. There was also no tumor case which had a large amount of DNA such as tetraploidy or over tetraploidy in the breast tumors so far examined here.

View full abstract

The histological examination of bone marrow in DDD mice, infected with diluted Friend leukemia virus, revealed such focal lesions as in the spleen. The focal lesions appeared as early as the spleen foci, when the liver was not involved. The hepatic lesions were considered secondary to the spleen and bone marrow ones.

View full abstract