Covalent Modification of Nuclear and Cytoplasmic Proteins of Hamster Embryo Cells During PAH Metabolism

摘要

It is well known that polynuclear aromatic hydrocarbons (PAH) are metabolized by mammalian cells to derivatives which covalently modify cellular macromolecules. Much effort has been devoted to defining the molecular structure of the major adducts formed with DNA in cells treated with benzo(a)pyrene (B(a)P). However, despite elucidation of the major pathways involved it has not been possible to unequivocally link the formation of specific adducts with the steps leading to malignant tranaformation. During the metabolism of B(a)P by hamster embryo cells (HECs), over 70% of the binding to nuclear macromolecules involves protein. Since nuclear proteins are known to play important roles in the structure of chromatin and are thought to be involved in the regulation of gene expression, the modification of these proteins by the introduction of PAH-adducts might reasonably be expected to perturb the structure and function of chromatin. Such perturbations could be involved in the processes which cause malignant transformation. Therefore, it seemed important to us to begin to define the pathways leading to protein-PAH binding in HECs treated with B(a)P. (ERA citation 06:001408)