| Autor: |
Tanabe P; Environmental Toxicology Graduate Program, University of California, Riverside, California92521, United States.; Department of Environmental Sciences, University of California, Riverside, California92521, United States., Pampanin DM; Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger4021, Norway., Tiruye HM; Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger4021, Norway., Jørgensen KB; Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, Stavanger4021, Norway., Hammond RI; Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, Illinois61801, United States., Gadepalli RS; Department of Biomolecular Sciences, The University of Mississippi School of Pharmacy, The University of Mississippi, University, Mississippi38677, United States., Rimoldi JM; Department of Biomolecular Sciences, The University of Mississippi School of Pharmacy, The University of Mississippi, University, Mississippi38677, United States., Schlenk D; Department of Environmental Sciences, University of California, Riverside, California92521, United States. |
| Abstrakt: |
Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) are ubiquitous contaminants that can be formed through oxidation of parent PAHs. Our previous studies found 2-hydroxychrysene (2-OHCHR) to be significantly more toxic to Japanese medaka embryos than 6-hydroxychrysene (6-OHCHR), an example of regioselective toxicity. We have also previously identified a sensitive developmental window to 2-OHCHR toxicity that closely coincided with liver development, leading us to hypothesize that differences in metabolism may play a role in the regioselective toxicity. To test this hypothesis, Japanese medaka embryos were treated with each isomer for 24 h during liver development (52-76 hpf). Although 6-OHCHR was absorbed 97.2 ± 0.18% faster than 2-OHCHR, it was eliminated 57.7 ± 0.36% faster as a glucuronide conjugate. Pretreatment with cytochrome P450 inhibitor, ketoconazole, reduced anemia by 96.8 ± 3.19% and mortality by 95.2 ± 4.76% in 2-OHCHR treatments. Formation of chrysene-1,2-diol (1,2-CAT) was also reduced by 64.4 ± 2.14% by ketoconazole pretreatment. While pretreatment with UDP-glucuronosyltransferase inhibitor, nilotinib, reduced glucuronidation of 2-OHCHR by 52.4 ± 2.55% and of 6-OHCHR by 63.7 ± 3.19%, it did not alter toxicity for either compound. These results indicate that CYP-mediated activation, potentially to 1,2-CAT, may explain the isomeric differences in developmental toxicity of 2-OHCHR. |
