Macrophage and interleukin-1 induced nitric oxide production and cytostasis in hamster tumor cells varying in malignant potential.
Nitric oxide has been shown to contribute to cytotoxicity in mouse and rat tumor cells. In these studies we examined the role of nitric oxide in cytostasis in hamster tumor cells varying in their malignant potential. Spontaneously transformed hamster embryonic fibroblasts (STHE cells) with low metastatic activity produced significantly greater amounts of nitric oxide in response to interleukin-1 (IL-1) or lipopolysaccharide (LPS)-activated hamster alveolar macrophages (HAM) than did tumor cell lines with high experimental metastatic activity (HET-SR, HET-SR1, STHE-83/20 cells). HET-SR cells, which exhibit low spontaneous metastastic activity, also produced relatively high levels of nitric oxide in response to IL-1, whereas the response of the spontaneously metastatic lines, HET-SR1 and STHE-83/20 cells, was low. IL-1 and HAM also induced cytostasis in nitric oxide-producing STHE and HET-SR cells. However, the nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), had no effect on this activity. These findings, together with the observation that anti-tumor necrosis factor alpha antibody prevented HAM-mediated cytostasis in all of the tumor cell lines demonstrate that nitric oxide is not involved in hamster macrophage-induced tumor cell growth suppression. In contrast to HAM, rat alveolar macrophages, which produced nitric oxide in response to LPS, exerted similar levels of cytostasis toward all of the hamster tumor cell variants, an action that was blocked by L-NMMA in HET-SR, HET-SR1, and STHE-83/20 cells. Thus production of nitric oxide by hamster tumor cells is inversely correlated with their malignant potential. However, nitric oxide does not appear to be involved in IL-1- or HAM-mediated cytostasis toward hamster tumor cells.
Lavnikova
N
N
Rutgers University, Piscataway, New Jersey 08855-0789, USA.
Burdelya
L
L
Lakhotia
A
A
Patel
N
N
Prokhorova
S
S
Laskin
D L
DL
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D006224:Cricetinae; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D008647:Mesocricetus; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000970:Antineoplastic Agents; D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide