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 covalent modifications of DNA, participation in redox cycling, and alterations in cellular signaling pathways. Similarly, exposure to ultraviolet (UV) light may modify DNA, generate reactive oxygen species, and alter signaling. Because environmental conditions may interact to affect cellular functions, we investigated the combined effects of benzo[a]pyrene (BaP) and UV light in a cell line in which BaP-induced alterations in Ca(2+) homeostasis have previously been shown. Exposure of MCF-10A cells to BaP (18 h) followed by a brief (5 min) exposure to UVA resulted in resistance to trypsinization of cells 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 fibers to substrate-associated aggregates of actin and caused depletion of cellular adenosine triphosphate (ATP). The effects of BaP+UVA on adhesion and actin aggregate formation were partially prevented by treatment with reduced glutathione. Depletion of cellular ATP affected resistance to trypsinization and actin organization in a similar manner. Thus, these studies suggest a redox-sensitive interaction between BaP+UVA light to deplete cellular ATP levels, resulting in resistance to trypsinization and actin filament reorganization in MCF-10A cells.
Seagrave
J C
JC
Lovelace Respiratory Research Institute, The University of New Mexico College of Pharmacy Toxicology Program, Albuquerque, NM 87131-1341, USA.
Burchiel
S W
SW
D000199:Actins / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000968:Antimycin A / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000528:radiation effects; D002452:Cell Count; D002460:Cell Line; D003599:Cytoskeleton / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D003847:Deoxyglucose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004533:Egtazic Acid / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D018384:Oxidative Stress; D014357:Trypsin / Q000494:pharmacology*; D014466:Ultraviolet Rays
D000199:Actins; D001564:Benzo(a)pyrene; D004533:Egtazic Acid; D000968:Antimycin A; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D014357:Trypsin; D005978:Glutathione