Involvement of NO, H2O2 and TNF-alpha in the reduced antitumor activity ofmurine peritoneal macrophages by aflatoxin B-1

Aflatoxin B-1 (AFB(1)), a potent hepatocarcinogen, has been known to impair non-specific and specific immune responses. Nitric oxide (NO), hydrogen pe roxide (H2O2), superoxide anion (O-2(-)) and tumor necrosis factor-alpha (T NF-alpha) produced by macrophages play an important role in host defense ag ainst tumors and microorganisms. In the present studies, we investigated th e involvement of those products in the reduced antitumor activities by AFB( 1). When macrophages are stimulated with LPS after AFB(1)-pretreatment, the cytolytic activities decrease in a dose-dependent manner. The addition of N-G-monomethyl arginine (NMMA), anti-TNF-alpha antibodies, catalase and per oxidase decreases antitumor activities further. In contrast, superoxide dis mutase (SOD) does not change the antitumor activities. NO and TNF-alpha pro duction was reduced by the addition of NMMA and anti-TNF-alpha antibodies, respectively. Taken together, these data indicate that the reduced antitumo r activities in murine peritoneal macrophages are mediated by the suppresse d production of NO, TNF-alpha and H2O2 by AFB(1) pretreatment, suggesting t hat the inhibitory effect of AFB(1) on those materials may provide the tumo rs with readily growing condition in vivo. (C) 1999 Elsevier Science Irelan d Ltd. All rights reserved.