Origin of pulmonary tumors in Buffalo rats induced by the subcutaneous injection of 4-nitroquinoline 1-oxide was investigated. Pulmonary tumors induced in 15 out of 70 rats were examined through serial sections to determine their relation to alveolar ducts, bronchus, and bronchiolus. For example, 19.3% of the tumors showed no relation to the bronchus, while 80.7% indicated direct relation to the bronchial epithelium. Several cases of focal metaplasia originating either from the alveolar area or from the bronchial epithelia were found.

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Chromosomes of mouse ascites hepatoma MH-134 and MH-129P maintained in the National Institutes of Health, Bethesda, Md, U.S.A., and Tohoku University, Sendai, Japan, were compared. MH-134A line maintained in Bethesda showed chromosome number variation from 38 to 47 with mode at 42. Most cells had a submedian metacentric and a minute as markers. Stemline cells of MH-134J subline maintained in Sendai had 40 chromosomes, including a median metacentric and a submedian metacentric chromosome with secondary constriction near the centromere. The mode of chromosome number variation in MH-129PA kept in Bethesda was at 46 including submedian metacentric with secondary constriction and minute markers, while that of MR-129PJ maintained in Sendai was at 45 chromosomes with one submedian metacentric, one submedian metacentric with secondary constriction, and one metacentric markers. All these lines were maintained using the same strain of mice and applying similar transplantation techniques. The cause of differentiation of the karyotypes in these lines maintained in different localities was discussed.

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Uptake of Acridine Orange by Ehrlich ascites carcinoma cells in tumor-bearing mice was studied after intraperitoneal administration of Nitromin, RC-4, Thio-TEPA, 6-mercaptopurine, 8-azaguanine, or Sarkomycin.
At higher doses (about the LD₅₀) an increase in Acridine Orange uptake per tumor cell was observed and this was roughly proportional to the increase in the number of cells staining with Eosin and to the morphological damage of the cells. The Acridine Orange uptake of the nuclear fraction was found to be greater than that of the mitochondrial fraction. At lower doses (about 1/30 of the LD₅₀), the Acridine Orange uptake per tumor cell tended to decrease after Nitromin or RC-4 treatment, although the number of cells staining with Eosin and morphological deformation of the cells increased. However, there was no significant difference in the Acridine Orange uptake between the nuclear and mitochondrial fractions of the treated and untreated groups.

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Comparative studies were made on the biological activities of toxohormone extracted from human malignant tumors and purified lipopolysaccharide derived from Salmonella typhimurium.
Marked depressions of both the liver catalase activities of mice and serum iron levels of rats occurred following single intraperitoneal injection of crude as well as fractionated toxohormone and of bacterial endotoxin, activity of the latter far exceeding the former.
However, a different response was observed when either of them was given by multiple subcutaneous injections over a prolonged period. Rats injected with toxohormone showed a profound decrease in the ferritin iron content in the liver when compared to the sham group injected with saline. On the other hand, rats injected with bacterial endotoxin did not show any significant alteration of hepatic ferritin iron content. A possible role of toxohormone as the cause for changes in iron metabolism observed in the tumor-bearing state is discussed.

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Alkaline phosphatase (EC. 3. 1. 3. 1, orthophosphoric monoester phosphohydrolase) and β-glucuronidase (EC. 3. 2. 1. 31, β-D-glucuronide glucuronohydrolase) activities in tumor-bearing rats and rats under given conditions are reported, especially from the viewpoint of the localization in the cell. From these data the metabolic regulatory mechanisms in the tumor-bearing rats were also discussed.
In this communication, a modified and more sensitive method for the assay of β-glucuronidase activity is also reported.

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Adenovirus type 12 was inoculated intraperitoneally, intrapleurally, intrapulmonarily, and subcutaneously into newborn hamsters. Most animals died of tumors in 30-60 days.
By sequential observations of the animals inoculated intraperitoneally or subcutaneously, it was found that the neoplastic change invariably developed along the fine peripheral nerve fibers about 10-35 days after virus inoculation.
The histologically well-developed tumors mainly showed a sarcomatous pattern while in parts such epithelial arrangements as trabecular, palisade, and/or rosettelike patterns were observed. These epithelial characteristics were more apparent in small tumor nodules in the early stage of development, as indicating the neuroectodermal origin of the tumor.
These observations suggested that the hamster tumors thus induced by adenovirus type 12 would be likely to have originated from neuroectodermal supporting cells.

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Reversible increase of intracellular accumulation of glycogen and oligosaccharides was observed in Yoshida sarcoma cells treated with a therapeutic dose of nitrogen mustard, in parallel with the appearance of cytomorphological effects on the tumor cells. The accumulation of the cell constituents became irreversible by repeated contact of the tumor cells with this agent in vitro, accompanied with acquisition of high resistance to the agent. These phenomena lasted for a long period through successive transplantation of the tumor to untreated rats.
The major component among the oligosaccharides was identified as maltose.

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Nicotinamide adenine dinucleotide-glycohydrolase (NADase) activity of Yoshida sarcoma cells was increased by various antitumor agents in vivo and in vitro at doses or concentrations scarcely enough to cause minimum cytomorphological changes of the tumor cells. On the contrary, NAD content itself was not significantly changed and NAD-pyrophosphorylase activity seemed to be rather suppressed by the treatment. It is worth noting that this increase of NADase activity was not observed with the liver of normal or tumor-bearing rats when treated with a dose effective to the tumor. It is also proved that the increase of the enzyme activity always occurred in the resistant strains of Yoshida sarcoma if the dose of the agent was increased just to the minimum effective dose of each of these resistant strains.

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4-Nitroquinoline 1-oxide was injected subcutaneously into rats. One, three, and 24 hours after the injection, the metabolites were extracted from injected site and purified by thin-layer chromatography. Two metabolites, main and minor, were identified as 4-aminoquinoline 1-oxide and 4-hydroxyquinoline 1-oxide.

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Study on the in vitro interaction between calf thymus DNA and tricycloquinazoline and its analog was carried out by using the flow dichroism measurement. Negative values of the differential dichroism were obtained and this shows that these carcinogens undergo direct interaction with DNA, orienting parallel to the planes of DNA bases. Extraction with organic solvent could remove these hydrocarbons from DNA, so the binding is not covalent. The ratios of binding of tricycloquinazoline and its analog were 1 molecule per 630 and 260 base-pairs, respectively. These findings were discussed in connection with the mechanism of carcinogenic action of these compounds, and the causal significance of the charge transfer due to the overlapping of π-orbitals of these carcinogens and DNA bases has been stressed.

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Changes in the activity and inductivity of glucose 6-phosphate dehydrogenase were studied histochemically in hepatic cells of rats fed 3'-methyl-4-dimethylaminoazobenzene. The activities of succinic dehydrogenase, choline dehydrogenase, glucan phosphorylase, and glucose 6-phosphatase, as well as lipid and glycogen contents were also examined in sections consecutive to those used for the study of glucose 6-phosphate dehydrogenase.
It was found that the activity of glucose 6-phosphate dehydrogenase and its inductivity decreased gradually in the order of regenerating cells, hyperplastic type I and II cells, and tumor cells. Similar decrease was also observed in the activities of some hydrolytic and oxidative enzymes.
Exceptions to this general tendency were, however, not uncommon; some hyperplastic cells and trabecular hepatoma cells showed an apparently higher glucose 6-phosphate dehydrogenase activity or its inductivity than did other hyperplastic and hepatoma cells. It was such cells that showed the activities of glucan phosphorylase and glucose 6-phosphatase and demonstrable amount of glycogen. These three cellular components were lacking in most tumor cells.

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Harvesting technique was applied to another cultured mammalian cells, Frukto, giving rise to a synchronous growth. Based on data of cycle parameters in synchronous and random population, it was detnonstrated that selective harvesting of mitotic cells assures a high degree of synchrony and conserves cell physiology in culture.

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