Nagoya Journal of Medical Science

An attempt was made to study the influences of anti-cancer agents on transtracheal tumor transplantation. For a preliminary investigation by the use of autoradiographic technique, the influence of Mitomycin C (MMC) was studied on DNA synthesis in epithelial cells of the rat trachea, which were regenerating following mechanical injury. A rapid increase of DNA synthesis in regenerating epithelial cells was observed from 6 hours to 18 hours after the injury. Maximum level of DNA synthesis was maintained from 18 to 48 hours, then decreased to the same level as observed at 6 hours. After intraperitoneal administration of MMC in the dose of 1/4 or 1/2 LD₅₀ immediately after the injury, DNA synthesis was remarkably depressed from 6 hours to 48 hours, whereas, the value at 72 hours increased significantly as compared with the control. In case of frequent intermittent administration of MMC at 1/4 LD₅₀ four time every other day before and once immediately after the injury, DNA synthesis was depressed for up to 72 hours and did not recover. Labelling index with ³H-Thymidine of epithelial cells of the normal trachea and bronchia was 0.5% and 0.4% respectively, and influence of MMC was not recognized except in the case of the above mentioned frequent intermittent administration. When subcutaneously growing tissue of Yoshida sarcoma was inoculated into the bronchia of rats by inhalation transtracheally, transplantation was not established in the bronchia. By frequent intermittent administration of MMC to the animals prior to inhalation, however, transtracheal transplantation was established at a rate of 30%. By microscopic study tumor cells were found to infIltrate the bronchial wall where the mucosa of the bronchia plugged by tumor tissue had peeled off. Proliferation of the tumor cells in the bronchia was manifested by the intracellular incorporation of ³H-Thymidine in the peripheral area of the tumor tissue which had plugged the bronchial canal.

I performed an experiment on the relationship between ¹⁴C-Bleomycin and Glutathione in vivo; especially on the relationship of radioactivity and antibacterial activity, and the results will be reported here.
1) When Bleomycin and Glutathione were administered simultaneously and animals were killed after 30 minutes, decrease in Bleomycin concentration in every organ was observed. The decrease rate in tumor was especially great (radioactivity: 80.3%, antibacterial activity: 78.4%).
2) When Glutathione is administered 15 minutes after administration of Bleomycin and the animals were sacrificed after 30 minutes, the decrease rate was highest in the skin followed by that in tumor and extremeiy low in the lung.
3) When Glutathion was given 30 minutes after Bleomycin administration and the animals sacrificed after 60 minutes, the decrease rate of intraorgan Bleomycin concentration was in the order of lung> tumor> skin.

We performed an experiment on the anticancer effect of Bleomycin and Glutathione administered simultaneously in tumor bearing mice.
1) The radioactivity of ³⁵S-Glutathione in organs tended to be lower after the simultaneous administration of the labelled Glutathione and Bleomycin than when the labelled Glutatione was given alone.
2) The reaction of Glutathione and Bleomycin in vivo depends upon the quantitative ratio of the two substances.
3) In cancer-bearing mice a comparison was made of anticancer effectiveness between Bleomycin used alone and in combination with Glutathione. During an initial 60 day period treatment with Bleomycin alone produced an excellent anticancer effect and also provided a marked life prolonging effect when compared with control. These effects in the Bleomycin + Glutathione group were no better than in the control group.
4) Past the 60th day of treatment (after 30 doses of Bleomycin or Glutathione were given) fatalities occurred frequently in the Bleomycin group due to the drug toxicity, while in the Bleomycin + Glutathione group a greater increment of survival time was attained due to a detoxifying effect of Glutathione.

In order to identify which papillary muscle recorded in a B-mode echocardiogram was the posterior or anterior one, 22 isolated canine hearts were cut through a cross-section identical with the B-mode echocardiogram. Hearts were carefully suspended horizontally in physiologic saline solution to prevent any change in their position. The papillary muscles were presumed to be echoes emerging from the left ventricular wall or protruding into the left ventricular cavity. In the experiment of cutting the posterior papillary muscle, eight papillary muscles of nine hearts were easily identified and cut almost in half longitudinally. In contrast, it was difficult to identify the anterior papillary muscle and in only four cases of 13 hearts was the papillary muscle cut almost in half longitudinally. However, nine anterior papillary muscles were cut somewhere in total. The papillary muscle was not detected it: one case and the cutting plane deviated from the papillary muscle in three hearts, medially in one and laterally in two cases. The B-mode echocardiogram of the identified posterior papillary muscle showed that it emerged from the left ventricular posterior wall and there was a wide space in front of it. In contrast, the anterior papillary muscle cut almost in half longitudinally protruded into the left ventricular cavity and showed a finger-like shape. There was a narrow space in front and behind.