Short-term moderate aflatoxin B-1 exposure has only minor effects on the gut-associated lymphoid tissue of Brown Norway rats

Aflatoxin B-1 (AFB(1)) is toxic to the systemic immune system in various an imal species, whereas little is known about ts effect on the gut-associated lymphoid tissue (GALT). It may be hypothesized that the toxicity of AFB(1) and its locally generated metabolites in the intestinal tissue may result in a disturbed intestinal integrity and, subsequently, in an impaired immun e response towards dietary proteins. The objective of our study was to inve stigate the toxic effect of short-term moderate AFB(1) exposure on the inte stinal epithelium and on the immune cells associated with the intestinal tr act. The toxicological potential of AFB(1) and its metabolites to the intes tinal epithelium was determined by measuring viability and genotoxic damage in isolated jejunal epithelial cells (comet assay) after 30 min incubation in vitro. In vivo toxicology studies were carried out with Brown Norway (B N) rats, which were exposed orally once a week with AFB, (1 x 100 mu g/kg b ody weight (b.w.)/week) for 5 consecutive weeks. Viability and genotoxicity were measured in explanted jejunal epithelial cells. For studying the effe ctiveness of AFB(1) on immunological parameters BN rats were treated with a high (study 1:1 x 1 mg/kg b.w./week) or a low (study 2:1 x 100 mu g/kg b.w ./week) AFB(1) dose for 5 consecutive weeks with or without ovalbumin (OVA) . Mesenteric lymphocytes were isolated and proliferative responsiveness, se cretion of interferon-gamma, and changes in lymphocyte subpopulations as we ll as mucosal mast cell specific protease and anti-OVA specific antibody co ncentrations were measured. In vitro, AFB(1) (> 30 mu M) induced genotoxici ty in rat jejunal epithelial cells. The oral administration of AFB(1) (1 x 100 mu g/kg b.w./week) did not induce DNA damage in jejunal epithelial cell s. The high AFB(1) dose increased the number of CD8+ and CD8/CD71+ cells in mesenteric lymph nodes. The immune response towards OVA was not affected. The low AFB(1) dose only reduced the proliferative responsiveness of mesent eric lymphocytes (P < 0.05). Serum concentrations of anti-OVA specific IgE antibody, of RMCPII, and the capacity of mesenteric lymphocytes to produce interferon-gamma were not impaired by AFB(1). In conclusion, exposure to mo derate doses of AFB(1) does not damage the intestinal epithelium and has on ly minor effects on the GALT. The low exposure, as it may predominantly occ ur in western countries, does not appear to increase the risk for sensitiza tion to dietary antigens. (C) 1999 Published by Elsevier Science Ireland Lt d. All rights reserved.