Aflatoxin B1 (AFB1), a potent hepatocarcinogen, is known to impair specific and nonspecific immune responses. Recent studies suggested that AFB1 affects macrophage functions. Macrophages play an important role in a host defense against tumors and bacteria. In addition, some macrophage products, including tumor necrosis alpha (TNF-alpha), can be cytotoxic. In the present study, we investigated the effect of aflatoxin B1 (AFB1) on LPS-induced TNF-alpha production by a mouse macrophage cell line, RAW 264.7 cells. Cells were pretreated with increasing concentrations of AFB1 for 2 hours followed by stimulation with lipopolysaccharide (LPS) for 6 h. The concentration of TNF-alpha released in the culture medium was assessed by enzyme-linked immunosorbent assay (ELISA). AFB1 at 1, 10, 50 or 100 µM reduced the production of TNF-alpha induced by LPS. Compared to vehicle control, there was a greater reduction of TNF-alpha production with increased concentration of AFB1 pretreatment and LPS stimulation. AFB1 at 100 µM decreased the synthesis of both TNF-alpha mRNA and protein in RAW 264.7 cells. To explore the mechanism of AFB1 activation by RAW 264.7 cells, we examined the expression of CYP3A4 and CYP3A11, two isoforms of cytochrome p450 known to activate AFB1. Our data indicated that CYP3A11 but not CYP3A4 was significantly expressed in RAW 264.7 cells. These results suggest that AFB1 pretreatment suppresses LPS-induced TNF production in RAW 264.7 cells. (Supported by NIH grant R01ES04139.)

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4378.