In vitro exposure of human lymphocytes to trichothecenes: Individual variation in sensitivity and effects of combined exposure on lymphocyte function

The trichothecenes are mycotoxins produced by fungi of the genus Fusarium, which are commonly present in foods and feed of cereal origin. Owing to the lack of sufficient toxicological data for most of the trichothecenes, in v itro studies may contribute to risk assessments of these toxins. In the pre sent report, human lymphocyte cultures were used to study the individual va riation in sensitivity among humans and the effects on in vitro Ig producti on. Furthermore, proliferative responses of cells exposed to combinations o f two of the toxins were studied. Four toxins, T-2 toxin, diacetoxyscirpeno l (DAS), nivalenol (NIV) and deoxynivalenol (DON) were included in the stud y. All four of the tested trichothecenes effectively inhibited mitogen-indu ced lymphocyte proliferation. There were no statistically significant diffe rences in sensitivity to the toxins between lymphocytes from female and mal e blood donors. The individual variation in sensitivity, evaluated as the r ange of IC50 values, was rather limited (within a factor of 3 to 4). Immuno globulin production by pokeweed-stimulated human lymphocytes was also effec tively inhibited with IC50 values similar to the IC50 values in the prolife ration tests for DON and NIV. However, IC50 values for Ig synthesis in cult ures exposed to T2 were approxi mately two to three times higher than the c orresponding IC50 values found in the proliferation tests. At low levels of exposure, elevated Ig production was observed in lymphocyte cultures from four out of the five blood donors tested. This effect was most pronounced o n IgA synthesis. Combinations of NIV with T2, DAS or DON resulted in additi ve toxicity in the lymphocyte proliferation test, while combinations of DON with T2 or DAS resulted in an inhibition that was slightly lower than what could have been expected from the inhibition produced by the individual to xins. In conclusion, the tested trichothecenes inhibited both proliferation and Ig production in human lymphocytes in a dose-dependent manner with lim ited variation in sensitivity between individuals. Enhanced Ig production w as observed in cell cultures exposed to the lower doses of the toxins. Comb ined exposure to two of the toxins resulted mainly in additive or antagonis tic effects, although synergistic effects cannot be excluded and should be further investigated. These findings indicate that the total intake of type A and B trichothecenes should be taken into account in risk assessments. ( C) 1999 Elsevier Science Ltd. All rights reserved.