2-4-diaminohypoxanthine and Lymphoma

In an analysis of nitric oxide (.NO) production and toxicity, chicken macrophage-generated .NO inhibited mitochondrial activity in both .NO-producing macrophages themselves and lymphoid tumor targets. However, differences in targeting of mitochondrial toxicity were observed among these cells. Two chicken macrophage cell lines, HD11 and MQ-NCSU, produced .NO (measured as nitrite) dependent upon concentrations of L-arginine and bacterial endotoxin (lipopolysaccharide). Mitochondrial activity was negatively correlated with the amount of .NO produced. Using a modified MTT assay, .NO induced suppression in two mitochondrial complexes. Mitochondrial activity was significantly suppressed among HD11 cells receiving LPS alone (complex I, 63.0 +/- 5.5% suppression; complex II, 27.9 +/- 5.2%). In contrast, mitochondrial activities in samples receiving LPS plus inhibitor, NG-nitro-L-arginine methyl ester (NAME; 5 mM) or 2,4-diamino-6-hydroxypyrimidine (DAHP; 5 mM), were not significantly different from control values. When HD11 macrophages were cocultured with lymphoblastoid tumor targets, RECC-CU60 (T cell) or LSCC-RP9 (B cell), adding LPS (1 microgram/ml), tumor cell mitochondrial activity was significantly suppressed. In the generator macrophages, complex I was more suppressed than complex II, whereas in lymphoid targets no such difference was observed. These results indicate that .NO inhibits complex I and II mitochondrial activity but that differential targeting can occur among chicken leukocyte populations.

Topics: Animals; Arginine; Cell Line; Cell Survival; Chickens; Hypoxanthines; Leukocytes; Lipopolysaccharides; Lymphoma; Macrophages; Mitochondria; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oxidoreductases; Tumor Cells, Cultured