The hemolytic component of cancer anemia: effects of osmotic and metabolic stress on the erythrocytes of rats bearing multifocal inoculations of the Walker 256 tumor

Cancer anemia is classified as an anemia of chronic diseases, although it is sometimes the first symptom of cancer. Cancer anemia includes a hemolytic component, important in the terminal stage when even transfused cells are rapidly destroyed. The presence of a chronic component and the terminal complications of the illness limit studies of the hemolytic component. A multifocal model of tumor growth was used here to simulate the terminal metastatic dissemination stage (several simultaneous inoculations of Walker 256 cells). The hemolytic component of anemia began 3-4 days after inoculation in 100 percent of the rats and progressed rapidly thereafter: Hb levels dropped from 14.9 +/- 0.02 to 8.7 +/- 0.06 from days 7 to 11 (~5 times the physiologically normal rate in rats) in the absence of bleeding. The development of anemia was correlated (r2 = 0.86) with the development of other systemic effects such as anorexia. There was a significant decrease in the osmotic fragility of circulating erythrocytes: the NaCl concentration causing 50 percent lysis was reduced from 4.52 +/- 0.06 to 4.10 +/- 0.01 (P<0.01) on day 7, indicating a reduction in erythrocyte volume. However, with mild metabolic stress (4-h incubation at 37§C), the erythrocytes showed a greater increase in osmotic fragility than the controls, suggesting marked alteration of erythrocyte homeostasis. These effects may be due to primary plasma membrane alterations (transport and/or permeability) and/or may be secondary to metabolic changes. This multifocal model is adequate for studying the hemolytic component of cancer anemia since it is rapid, highly reproducible and causes minimal animal suffering.

Fatty acid oxidation in lymphocytes from Walker 256 tumor-bearing rats

The oxidation of fatty acids in lymphocytes from the mesenteric lymph nodes of Walker 256 carcinosarcoma-bearing rats (TB) was studied, as well as the activity of the mitochondrial long-chain fatty acid transport system. Two-month old Wistar rats were subcutaneously implanted with 10(7) cells and after 2 weeks the tumor mass was 15-20 per cent of the carcass weight. The activity of camitine palmitoyltransferase (CPT) II was demonstrable in the lymphocytes of the TB group (8.2 ñ 5.6 nmol/min per mg mitochondria protein for 15 rats) and was not detected in the control, while that of CPT I was only slightly increased in the former. Similar rates of [1-14C]-palmitate decarboxylation were found for TB and control rat lymphocytes. However, when the rate of decarboxylation of [1-14C]-paimitate present in the intracellular pool of lipids was investigated in cultured lymphocytes, the cells of TB rats exhibited rates 17-fold higher than those of control animals in the presence of fetal calf serum (FCS). Decarboxylation in the presence of TB rat serum was 178-fold higher than obtained with normal rat serum, and 1.4-fold compared to FCS. These results suggest that, during cachexia, lymphocytes preferably oxidize intracellular lipids, and that this capacity is greatly enhanced by factors circulating in the serum of tumor-bearing rats.

Alteraçöes da hemostasia em alguns tumores experimentais / Hemostatic changes in some experimental tumors

As alteraçöes hemostásicas em animais portadores de tumores de Ehrlich, Krebs e do carcinoma Walker-256 foram avaliadas pelo tempo de protrombina de Quick e pelo tempo de tromboplastina parcial ativada. Nos animais portadores da forma sólida desses tumores, o tempo de protombina foi sempre igual aos dos grupos-controles. Nos animais portadores das formas ascíticas, o tempo de protombina esteve aumentado, enquanto o tempo de tromboplastina parcial esteve normal nos tumores de Krebs e Ehrlich e aumentado no tumor de Walker-256