Effect of differential hypothermia on adenovirus type 12 induced tumors -Histological and histochemical study-

Differential hypothermia (D. H.) for the treatment of brain tumor, a method in which the tumor is kept normothermic while the body is kept hypothermic (Popovic et al., 1965) was examined. In order to clarify the effect of D. H. on tumor metabolism, histological and histochemical examinations were performed on adenovirus type 12 induced tumors transplanted into the cheek pouches of 50 Syrian golden hamsters. The animals were anesthsized with 5% pentobarbital sodium given intraperitoneally. The tumors were immersed in a warm water bath to keep the tumor temperature at 37℃ while the total body was kept hypothermic (12℃) by placing it in ice water for 10 hours. Tumor growth was examined in 20 animals. Fifty percent of the tumors disappeared completely with no regrowth within 1 month after D. H., and 35% showed marked regression. However 15% showed no regression.Histological and histochemical examinations performed on 30 animals disclosed degenerative changes of the tumors treated with D. H., such as enlarged lumen of blood vessels and edema around tumor cells immediately after the treatment. Pyknoses and karyorrhexes became obvious 24 hours after the treatment. Histochemical examinations were performed immediately, 12, 24, 48 and 96 hours after D. H. Three hydrolytic enzymes [alkaline phosphatase (ALP) and acid phosphatase (ACP), Burstone's method, and adenosine triphosphatase (ATPase) Wackstein-Meisel's method] and 8 glycolytic enzymes [lactate dehydrogenase (LHD), malate dehydrogenase (MDH), glucose-6-phosphate dehydrogenase (G-6-PHD) and β-hydroxybutyrate dehydrogenase (β-HDH), Mori's method, succinate dehydrogenase (SDH), Nachlas's method, cytochrome oxidase (CYO), Burston's method, glutamate dehydrogenase (GDH), Barka-Anderson's method, and monoamine oxidase (MAO), Glenner, Burster and Brown's method] were examined.Enzymatic activities of LDH and MDH obviously decreased in the tumor cells immediately after D. H. and also slightly but significantly thereafter. On the other hand, the activities of β-HDH, SDH, CYO, GDH and MAO obviously increased in the tumor cells up to 12 hours after D. H. These results indicate that acceleration of fatty acid and amino acid metabolism and aberrant glycolysis occurs. These metabolic changes are suggestive of degenerative changes of tumor cells following D. H. ALP, ACP, ATPase and G-6-PDH showed no activity in the tumor cells before or after D. H. In the tumor stromas, the activities of ALP and ACP increased immediately and over 24 hours after D. H. The activity of ATPase was confined only to the endothelium of blood vessels and decreased up to 48 hours after D. H. These changes in ALP, ACP and ATPase activity in the tumor stromas suggest metabolic disturbances and increased permeability of the blood vessel walls following D. H. The other enzymes showed no remarkable changes in the tumor stromas after D. H.