Photo-induced formation of DNA adducts of 2,2',4,4',5,5'-hexachlorobiphenyl in cultured human cells

Association of the PCB congener 2,2',4,4',5,5'-hexachlorobiphenyl (6-CB) with cell nuclei has been studied in cultured monolayer human Chang liver cells. Photo-induced formation of covalent bonds determined 6-CB binding to protein of cell nuclei and to DNA. Nuclear binding of 6-CB approached equilibrium after approximately 30 min of incubation. Photo-induced binding in vitro to purified Chang liver cell DNA substantiated direct interaction of the PCB congener with DNA. In monolayer cells, low levels of photo-induced 6-CB DNA adducts could be detected using the very sensitive 32P-postlabeling method. Adduct formation was dependent on 6-CB concentration as well as on incubation time. Highest adduct levels were in the range of 2 X 10(-8). Model reactions in vitro showed photo-induced binding of 6-CB to individual purine deoxyribonucleotide-3'-phosphates. The results demonstrate rapid intracellular movement of the PCB congener into the cell nucleus. The vast majority is associated with nuclear protein, minute amounts of 6-CB are found proximate to the DNA helix as evidenced by photo-induced adducts of purine nucleotides.