To investigate the mechanism of local coagulation observed in some tumor tissues or initial metastatic foci, quantitative and comparative study was carried out on the coagulation activities of tumor cells and tumor tissues in various strains of rat ascites hepatoma. The content of thromboplastin was expressed as the relative concentration against that in the brain tissue. It appeared obvious that ascites hepatoma cells of each strain have different amounts of coagulant(s) considered as tissue thromboplastin as well as anticoagulant compounds. A large amount of thromboplastin was contained in tumor cells of AH-130, AH-408, and AH-44, but only a small amount in AH-62F, Yoshida sarcoma, and AH-7974F. A high level of thromboplastin content in subcutaneous form of Yoshida sarcoma cells was observed, compared with that in ascitic form, and it was suggested that the high coagulation activity of tumor tissue does not necessarily reflect the high activity of tumor cells. The possible role of thromboplastin contained in tumor cells is discussed.

View full abstract

A study of the large intestine in 1, 000 autopsy subjects yielded 95 patients (9.5%) with 127 adenomas. This frequency was significantly higher than that of hypertrophic mucosal protrusion (3.5%), juvenile-type polyp (0.3%), Peutz-Jeghers type polyp (0.2%), and hyperplasia (metaplasia) (1.1%). Adenoma increased in frequency with advancing age, appearing in 33.3% of octogenarians. The right colon (51.2%) was the most frequent site, followed by the distal transverase and descending colon (23.6%). The adenomas were found in the sigmoid colon or rectum in 18% of subjects. Analysis of the age distribution of 116 surgical patients with 150 adenomas revealed that satellite polyps were most numerous between 60 and 69 years of age, whereas adenomas in noncancerous bowel were most frequently observed in the 40's. Histological atypia was related to the size and location of adenomas. In the autopsy series atypia was most prominent in the lower large bowel. Adenomas of the surgical series, obtained mostly from the lower tract, generally showed advanced atypia. Adenomas with focal malignancy were found in 13.3% of the surgical series but rose to 32.6% in adenomas of over 10mm in diameter. The incidence of focal malignancy in adenomas was 21.4% in females and 14.1% in males.

View full abstract

A transplantable pregnancy-dependent mammary tumor line was established in DDD mice and designated as TPDMT-4. Tumor implants did not grow to a palpable size but survived long in virgins. In contrast, tumors grew during pregnancy and regressed rapidly after parturition, reaching ascending peaks in successive pregnancies in breeders. Tumors continued to regress to a fixed volume when hosts were not mated after parturition. The tumors showed different morphology at different stages. (i) In mid-pregnancy, they were characterized by uniform acinar structures formed by small cuboidal epithelial cells. (ii) These structures became obscure in late pregnancy because of high cellularity with degenerative changes and secretory activity. (iii) Tumors had glandular or cystic lumens filled with milky material after parturition. (iv) They showed a tubular and papillary architecture which was composed of single-layered peculiar columnar cells in postpartum hosts where they regressed to a minimum size. (v) Multi-layered cuboidal and columnar cells forming a tubular and papillary structure remained after transplantation in virgins. Preliminary study suggests that mammotropin and progesterone may be important for proliferation of tumor cells of this line.

View full abstract

The herb extract of Capsella bursa-pastoris (Cruciferae) was examined for its effect on the hepatocarcinogenesis in the rats fed 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB). Male Donryu rats were given 0.5g of 3'-Me-DAB by being fed a diet containing 0.06% 3'-Me-DAB, and then they were given drinking water containing the herb extract in 0.2% with a basal diet for 258 days. Administration of the herb extract brought a complete inhibition of hepatoma induction, accompanied by a markedly reduced development of cholangiofibrosis, bile duct cell proliferation, and hepatic cell degeneration.

View full abstract

Three undifferentiated adenocarcinomas induced in rats by oral administration of N-methyl-N'-nitro-N-nitrosoguanidine or 4-nitroquinoline 1-oxide combined with surfactants were studied with light and electron microscope. There were three types of cancer cells, i.e., mucin-containing cell, intracellular microcyst cell, and poorly differentiated mucous cell. The mucin-containing cell was closely packed with a large amount of mucin, thus rendering a signet-ring appearance. Under electron microscope, the mucin-containing cells were classified further into two subtypes; one contained pale, large, and mutually fused mucin granules resembling those of the goblet cell, and the other had dark, mostly small and discrete granules like those of the surface or pit mucous cell.
The intracellular microcyst cell revealed a small cystic luminal structure in the cytoplasm. The wall of the microcyst was lined with microvilli projecting into the lumen. When the microcyst became distended, the cell exhibited a signet-ring appearance.
The poorly differentiated mucous cell had a large nucleus and abundant quantity of free ribosomes scattered throughout the cytoplasm.

View full abstract

As an animal model to study the etiological significance of the adenoviruses isolated from human tumors or cancer patients, adenovirus type 12 (ad-12), an oncogenic type, and type 6 (ad-6), a non-oncogenic type, were inoculated into hamsters simultaneously or at some intervals, and the recovery of viruses from tumors and the liver was tried. From tumors, neither ad-12, the causative agent of tumors, nor ad-6, non-causative agent, was recovered. From the liver, only ad-6 was recovered. It thus appears that, in hamsters, ad-12-induced tumors yield neither the causative nor non-causative "passenger" adenovirus, though tissues other than tumors might yield non-causative "passenger" adenovirus. When inoculated simultaneously with or 2 days after ad-12, ad-6 inhibited the tumor induction by ad-12. This inhibitory effect was not observed when ad-6 was inoculated 4 or more days after ad-12, suggesting that this inhibitory effect of ad-6 would be due to its cytocidal effect on the target cells of ad-12 and that, once transformed by ad-12, cells become resistant to ad-6 and form tumors.

View full abstract

After subcutaneous inoculation of Ehrlich carcinoma cells, complete regression of tumors was observed in 507 of 1429 dd/Y mice which were given intradermal injections of a lipopolysaccharide from Proteus vulgaris. Sera from resistant mice obtained four weeks after challenges with tumor cells showed neutralizing activity in vivo against Ehrlich carcinoma cells, and sarcoma-180 and MM2 cells, but not against SR-DDD or MH-134 tumor cells. These sera showing neutralizing activity in vivo did not show either complement-dependent cytotoxicity or agglutinating activity against Ehrlich carcinoma cells in vitro. The neutralizing activity was not inhibited by anti-mouse immunoglobulin-G and -M sera. In resistant mice, the growth of tumor cells in diffusion chambers was partially inhibited without cell-mediated responses, but transplantability of the cells in the chambers was unaffected. Incubation of Ehrlich carcinoma cells with these sera from resistant mice to allow absorption did not alter their neutralization titers. These results demonstrate that a humoral factor other than a conventional antibody is involved in the regression of Ehrlich carcinoma in these mice, and that one of the antitumor actions of this lipopolysaccharide is to increase production of this factor.

View full abstract

A single subcutaneous administration of 50μg of N-2-fluorenylacetamide (FAA) or 25μg of N-hydroxy-2-fluorenylacetamide to newborn ICR/JCL mice induced liver tumors in males (16-72%). The age of injection after birth was an important factor in FAA hepatocarcinogenesis.

View full abstract

Ultrastructural changes induced by Carbazilquinone in L-1210 lymphocytic leukemic cells infiltrated in mice were observed in the liver by electron microscopy. After 72hr, majority of the cells contained numerous nuclei which were of irregular shape tending to form nuclear projections.

View full abstract

Numerous microvilli were observed on the surface of cultured mouse mammary carcinoma cell line (FM3A/B) and its non-transplantable variant (M6) by scanning electron microscopy. These microvilli were similar in number and shape in the two strains but those of M6 cells were slightly more slender than those of FM3A/B cells.

View full abstract

Macroautoradiographic studies on the distribution of ¹⁴C-labeled N-methyl-N'-nitro-N-nitrosoguanidine (MNNG-¹⁴C) in mice revealed that radioactivity derived from MNNG distributed selectively in nerve tissues 1hr after intravenous administration but not 5hr later. Such a phenomenon cannot be seen after oral administration.

View full abstract

The rat liver microsomal acetylesterase activity increases in the early stage of tumor bearing and then decreases markedly in the advanced stage. The mechanism of this biphasic change was studied and it was found that the hypoalbuminosis and glucocorticoid seem to be responsible.

View full abstract

Combined administration of N-methyl-N'-nitro-N-nitrosoguanidine and surfactants, which have been commonly used in commercial foods, cosmetics, drugs, and dentifrices, induced many adenocarcinomas including a few undifferentiated types and several sarcomas in the glandular stomach of rats.

View full abstract

Thirty-five female Donryu rats were given continuously 400-ppm solution of 1-ethyl-1-nitro-ourea as their drinking water. Among them, 34 rats (97%) developed erythroleukemia beween 70 and 113 experimental days, 86.4±10.4 days in the average. No other tumors were letected in any of them.

View full abstract

Oxygenation of benzo[a]pyrene occurred when a chemical model system, (CF₃COOH+H₂O₂), was used as a model for the arylhydrocarbon hydroxylase. Two compounds among the products were identified as 6-oxybenzo[a]pyrene radical and 3-hydroxybenzo[a]pyrene which have been proved to be metabolites of benzo[a]pyrene in the animal body.

View full abstract