Activation of respiratory burst in human granulocytes by polychlorinated biphenyls: A structure-activity study.
The respiratory burst in human granulocytes activated by 33 different congeners of polychlorinated biphenyls (PCBs) was measured as luminol-amplified chemoluminescence. The selection of 20 (training set) compounds was based on multivariate chemical characterization, laying the groundwork for covering the whole chemical series of tetra- through hepta-chlorinated PCBs. In addition 6 congeners were used as a validation set, and 7 were mono- to tri-chlorinated congeners representing low-chlorinated compounds not covered by the 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 size 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 molecule and respiratory burst activity. Congeners with a 2,4, 6-substitution on one biphenyl ring are optimal activators. In conclusion, all three factors, size, rotation, and electronic properties, which are not independent of each other, are important for the activity of the PCBs.
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Division for Environmental Toxicology, Norwegian Defence Research Establishment, Kjeller, N-2027, Norway.
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Andersson
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D004785:Environmental Pollutants / Q000633:toxicity*; D006098:Granulocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008163:Luminescent Measurements; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000633:toxicity*; D016897:Respiratory Burst / Q000187:drug effects* / Q000502:physiology; D013329:Structure-Activity Relationship
D004785:Environmental Pollutants; D011078:Polychlorinated Biphenyls