Interactions between benzo[a]pyrene and UVA light affecting ATP levels, cytoskeletal organization, and resistance to trypsinization

Polycyclic aromatic hydrocarbons affect cells in many ways, including coval ent modifications of DNA, participation in redox cycling, and alterations i n cellular signaling pathways. Similarly, exposure to ultraviolet (UV) ligh t may modify DNA, generate reactive oxygen species, and alter signaling. Be cause environmental conditions may interact to affect cellular functions, w e investigated the combined effects of benzo[a]pyrene (BaP) and UV light in a cell line in which BaP-induced alterations in Ca2+ homeostasis have prev iously been shown. Exposure of MCF-10A cells to BaP (18 h) followed by a br ief (5 min) exposure to UVA resulted in resistance to trypsinization of cel ls grown on type I collagen (Vitrogen). This effect was not seen following treatment with BaP or UVA alone nor with benzo[e]pyrene (BeP) + UVA. BaP UVA light also caused actin filaments to reorganize from typical stress fib ers to substrate-associated aggregates of actin and caused depletion of cel lular adenosine triphosphate (ATP). The effects of BaP + UVA on adhesion an d actin aggregate formation were partially prevented by treatment with redu ced glutathione. Depletion of cellular ATP affected resistance to trypsiniz ation and actin organization in a similar manner. Thus, these studies sugge st a redox-sensitive interaction between BaP + UVA light to deplete cellula r ATP levels, resulting in resistance to trypsinization and actin filament reorganization in MCF-10A cells. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.