Inhibition of respiration of tumor cells by methylglyoxal and protection of inhibition by lactaldehyde

The effect of methylglyoxal (MG), ascorbic acid and lactaldehyde has been tested on the in vitro respiration of Ehrlich ascites carcinoma (EAC) cells and several normal and malignant human tissues. Methylglyoxal inhibited the respiration of each type of malignant cell and tissue tested, but it had practically no inhibitory effect on the respiration of any of the normal cells and tissues. Ascorbic acid exhibited a synergistic effect with MG in inhibiting the respiration of all the neoplastic cells. In the presence of lactaldehyde, a catabolite of MG, the inhibitory effect of MG on the respiration of tumor cells was significantly reduced. Lactaldehyde can exert a similar protective effect on the loss of viability and transplantability of MG-treated EAC cells.     

Impaired mitochondrial respiration and stimulated glycolysis by m-iodobenzylguanidine (MIBG)

m-Iodobenzylguanidine (MIBG) is a functional analogue of the neurotransmitter norepinephrine. Radio-iodinated 131I-MIBG is used clinically as a tumor-targeted radiopharmaceutical agent in the diagnosis and treatment of adrenergic tumors. Native MIBG has previously been demonstrated to be cytotoxic in cultured cells and to produce anti-tumor responses in animals when non-toxic schedules are used. In this study the effect of MIBG was investigated on isolated rat liver mitochondria and on various tumor cell lines (human neuroblastoma SK-N-SH, mouse neuroblastoma N1E115 and mouse lymphosarcoma S49). Results revealed that MIBG inhibits respiration of isolated liver mitochondria at complex I of the respiratory chain, without affecting F1 ATP-ase. In cell lines, impairment of the mitochondrial respiration was evident from reduced oxygen consumption and decreased intracellular ATP levels. In response to this effect, the glycolytic flux was stimulated as shown by increased glucose consumption and lactic acid production. Cytotoxicity of MIBG was proportional to drug-induced alterations in glucose metabolism.     

The impairment of respiration by glycolysis in the Lewis lung carcinoma

Isolated vegetative tumour cells from mice bearing the Lewis lung carcinoma showed low rates of basal respiration with both low oxygen uptake rates and cytochrome-c oxidase activity. The cells were affected by a marked Crabtree effect and a high rate of lactate production in the presence of 10 mM glucose. The glycolytic capacity of the tumour was also assessed through the measurement of the maximum activities for hexokinase, phosphofructokinase, pyruvate kinase and lactate dehydrogenase. These activities were similar to the ones found in other fast-growing, undifferentiated tumours. The concentration of fructose-2,6-bisphosphate in the tumour was 2,3 nmoles/g fresh tissue wt., a value which is of the same order of magnitude as that found in other types of highly glycolytic cells. It is concluded that the Lewis lung carcinoma follows the same pattern as other undifferentiated tumours with a high capacity for both glucose and amino acid utilization.     

β-胡萝卜素对小鼠Ehrlich腹水癌的抑制作用

 实验观察β-胡萝卜素(β-Carotene, β-C)对Ehrlich腹水癌(EhrlichAscitesCarcinoma, EAC)小鼠生命延长率的影响, 发现β-C5mg, 7．5mg·Kg^-1明显提高EAC小鼠的生命延长率和增加胸腺指数和脾脏指数(均为P＜0.05), β-C各剂量组(2.5mg, 5mg, 7.5mg·Kg^-1)均能促进有丝分裂原PHA诱导的淋巴细胞增殖(低剂量组为P＜0.05, 中剂量组和高剂量组均为P＜0.01)。 结果表明, β-C对EAC具有抑制作用, 且这一作用与其促进肿瘤免疫有关。     

Changes in SCM-responses of lymphocytes in mice after implantation with ehrlich ascites cells

BDF-1 mice implanted for various times and with different numbers of Ehrlich ascites cells were used as a model system to find out how early in the development of neoplasia the SCM-responding subpopulation of lymphocytes can detect cancer (SCM-test), as assessed by changes in intracellular fluorescein polarization in response to stimulation with phytohaemagglutinin and ascites cell extract (ACE). One hour after implantation of 7.5 × 10⁵ ascites cells SCM-responses to ACE were induced and PHA responses abrogated. At the threshold number of 3.5 × 10⁵ ascites cells per animal SCM-responses to both ACE and PHA were observed. Ascites cells killed by radiation did not induce changes in SCM-responses. Extrapolation of these data on the basis of body weight ratio indicates that a human tumour load of less than 10⁹ cancer cells might be detectable in the SCM-test.     

THE INHIBITORY EFFECT OF EXTRACT OF CAMELLIA SINENSIS AND EXTRACT OF CAMELLIA PTILOPHYLLA CHANG ON DNA POLYMERASE OF EHRLICH ASCITES CARCINOMA CELLS

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Lipid analysis of cell nuclei in young and old ehrlich ascites tumors

The total lipid content of whole cells and isolated nuclei of Ehrlich ascites tumors was found to increase in parallel with increasing age. Mainly triglycerides were accumulated both in the cells and in the nuclei, but the nuclear fraction showed also an increase in the total cholesterol content. No marked accumulation of lipid droplets could be observed in isolated nuclei, and thus it can be presumed that in the course of aging the increase in neutral lipid content is due to a profound alteration in the lipid composition of lipid-containing nuclear structures.