| Title: | Benzo[a]pyrene diones are produced by photochemical and enzymatic oxidation and induce concentration-dependent decreases in the proliferative state of human pulmonary epithelial cells |
| Author(s): | Reed M; Monske M; Lauer F; Meserole S; Born J; Burchiel S; |
| Address: | "Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA. mreed@lrri.org" |
| Journal Title: | J Toxicol Environ Health A |
| ISSN/ISBN: | 1528-7394 (Print) 0098-4108 (Linking) |
| Abstract: | "Organic components within mixtures of combustion-derived materials may play an important role in the correlation between air pollution and adverse cardio/respiratory health. One class of these organic components, polycyclic aromatic hydrocarbons (PAHs), has been shown to produce a wide variety of adverse health effects. An air toxic and a model PAH, benzo[a]pyrene (BaP), is a component of combustion-derived particulate matter (PM). Although most biological effects associated with BaP have been attributed to the cytochrome P-450 derived BaP 7,8-diol 9,10-epoxide, many other BaP oxidation products are formed in atmospheric and biological reactions and may contribute to PAH-induced adverse health effects. In an ambient environment, BaP and other PAHs undergo oxidation in the presence of ultraviolet light, O(2), O(3), NO(2), or OH(*). Biological peroxidase- and P-450 mediated conversion of BaP produces an extensive metabolic profile of BaP oxidation products that significantly outnumber the 7,8-diol/diol epoxide. The data herein show that in addition to near-ultraviolet light and P-450 isozymes, lactoperoxidase (airway peroxidase) converted BaP into a mixture of three diones, the 1,6-, 3,6-, and 6,12-BaP dione (BPD). In addition, it was found that low concentrations of BPDs induced a concentration-dependent decrease in the proliferation state of human pulmonary epithelial cells in vitro. Nanomolar concentrations of BPDs mediated cell growth inhibition, which was partially reversed by co-incubation with N-acetyl-L-cysteine and ascorbate. BPDs induced the formation of reactive oxygen species as measured by the fluorophore 2,7-dichloro-fluorescein. Together, these results may indicate a role for PAH oxidation products (PAH diones) in the adverse health effects associated with combustion-derived PM and semivolatile organic compounds" |
| Keywords: | "Benzo(a)pyrene/adverse effects/*chemistry Cell Culture Techniques Cytochrome P-450 Enzyme System/pharmacology Dose-Response Relationship, Drug Epithelial Cells/*drug effects/physiology Humans Lung/cytology/*pathology Oxidation-Reduction Photochemistry Vol;" |
| Notes: | "MedlineReed, Matthew Monske, Michael Lauer, Fredine Meserole, Stephen Born, Jerry Burchiel, Scott eng R01 ES-05495/ES/NIEHS NIH HHS/ R01 ES-07259/ES/NIEHS NIH HHS/ Research Support, U.S. Gov't, P.H.S. England 2003/07/10 J Toxicol Environ Health A. 2003 Jul 11; 66(13):1189-205. doi: 10.1080/15287390306409" |
