Activation of respiratory burst in human granulocytes by polychlorinated biphenyls: A structure-activity study

The respiratory burst in human granulocytes activated by 33 different conge ners of polychlorinated biphenyls (PCBs) was measured as luminol-amplified chemoluminescence. The selection of 20 (training set) compounds was based o n multivariate chemical characterization, laying the groundwork for coverin g the whole chemical series of tetra- through hepta-chlorinated PCBs. In ad dition 6 congeners were used as a validation set, and 7 were monoto tri-chl orinated congeners representing low-chlorinated compounds not covered by th e training set. Only ortho-substituted biphenyls activate respiratory burst . There is a correlation between activated respiratory burst and the total surface area of congeners up to 230 x 10(-20) m(2). Congeners of larger siz e show a reduced activity. There is also a correlation between respiratory burst activity and the number of ortho-substituents. Furthermore, there is also a correlation with parameters that describe absolute hardness of the m olecule and respiratory burst activity. Congeners with a 2,4,6-substitution on one biphenyl ring are optimal activators. In conclusion, all three fact ors, size, rotation, and electronic properties, which are not independent o f each other, are important for the activity of the PCBs. (C) 2000 Academic Press.