Surveys have shown that AFB1 is frequently found in respirable grain dust (up to 43,700 ppb) and that the serum of occupational workers exposed to contaminated dust contains AFB1-albumin adducts. The investigators' data demonstrate that respiratory exposure of rodents to AFB1 impairs the alveolar macrophage (AM) phagocytic defense system. The results indicate that respiratory exposure to AFB1 should be considered a human health risk is associated with diseases resulting from impaired lung defenses where exposure to AFB1-laden dusts is common. Indeed, through its effect on lowered lung resistance, AFB1 exposure poses a more wide ranging and insidious health hazard than its genotoxic endpoint. It is well established that oral exposure to AFB1 impairs a wide spectrum of systemic host defenses however, the mechanism of this effect have not been addressed. The observation that oral AFB1 Impairs the antibody response to a T-dependent antigen but not to a T-independent antigen provides a clue to the mechanism by indicating that AFB1 has an effect on T-lymphocytes. Critical to the evaluation of the magnitude of human risk from inhalation of AFB1-contaminated grain dust is an experimental data base. However, the full biologic effect of respiratory exposure to AFB1 on lung defenses is not known nor are the mechanisms involved. The goal of the proposed research is to define the cellular mechanisms of AFB1-induced suppression of pulmonary defenses and elucidate the consequences of such impairments. The overall hypothesis of this application is that respiratory AFB1 exposure regulates the innate and acquired immune responses though alterations of the functional capacity of the antigen presenting cells, and the T-lymphocyte repertoire of the immune response. Also, data-response relationships between inhalation to AFB1- laden grain dust that estimate occupational exposure and the most sensitive parameters of altered immune response will define the no effect level. These studies will establish the experimental data base required for the development of a risk assessment model of human populations exposed to AFB1-contaminated grain dust. This data base can then be used as a guide to focus epidemiologic studies toward a more complete assessment of the health hazard of occupational inhalation exposure to AFB1-laden grain dust.
