PUBLICATION
Zebrafish CYP1A expression in transgenic Caenorhabditis elegans protects from exposures to benzo[a]pyrene and a complex polycyclic aromatic hydrocarbon mixture
- Authors
- Harris, J.B., Hartman, J.H., Luz, A.L., Wilson, J.Y., Dinyari, A., Meyer, J.N.
- ID
- ZDB-PUB-200504-7
- Date
- 2020
- Source
- Toxicology 440: 152473 (Journal)
- Registered Authors
- Keywords
- Benzo[a]pyrene, Carcinogenic metabolites, Cytochrome P450s, DNA damage, Nucleotide excision repair, Polycyclic aromatic hydrocarbons
- MeSH Terms
-
- Adenosine Triphosphate/metabolism
- Animals
- Animals, Genetically Modified
- Benzo(a)pyrene/antagonists & inhibitors*
- Benzo(a)pyrene/toxicity*
- Caenorhabditis elegans/metabolism*
- Cytochrome P-450 CYP1A1/genetics*
- Cytochrome P-450 CYP1A1/metabolism
- DNA Repair/drug effects
- Embryo, Nonmammalian
- Larva/drug effects
- Larva/growth & development
- Molecular Weight
- Polycyclic Aromatic Hydrocarbons/antagonists & inhibitors*
- Polycyclic Aromatic Hydrocarbons/toxicity*
- Reproduction/drug effects
- Water Pollutants, Chemical/toxicity*
- Zebrafish/metabolism*
- PubMed
- 32360973 Full text @ Toxicology
- CTD
- 32360973
Citation
Harris, J.B., Hartman, J.H., Luz, A.L., Wilson, J.Y., Dinyari, A., Meyer, J.N. (2020) Zebrafish CYP1A expression in transgenic Caenorhabditis elegans protects from exposures to benzo[a]pyrene and a complex polycyclic aromatic hydrocarbon mixture. Toxicology. 440:152473.
Abstract
Polycyclic aromatic hydrocarbons (PAHs) are environmental toxicants primarily produced during incomplete combustion; some are carcinogens. PAHs can be safely metabolized or, paradoxically, bioactivated via specific cytochrome P450 (CYP) enzymes to more reactive metabolites, some of which can damage DNA and proteins. Among the CYP isoforms implicated in PAH metabolism, CYP1A enzymes have been reported to both sensitize and protect from PAH toxicity. To clarify the role of CYP1A in PAH toxicity, we generated transgenic Caenorhabditis elegans that express CYP1A at a basal (but not inducible) level. Because this species does not normally express any CYP1 family enzyme, this approach permitted a test of the role of basally expressed CYP1A in PAH toxicity. We exposed C. elegans at different life stages to either the PAH benzo[a]pyrene (BaP) alone, or a real-world mixture dominated by PAHs extracted from the sediment of a highly-contaminated site on the Elizabeth River (VA, USA). This site, the former Atlantic Wood Industries, was declared a Superfund site due to coal tar creosote contamination that caused very high levels (in the [mg/mL] range) of high molecular weight PAHs within the sediments. We demonstrate that CYP1A protects against BaP-induced growth delay, reproductive toxicity, and reduction of steady state ATP levels. Lack of sensitivity of a DNA repair (Nucleotide Excision Repair)-deficient strain suggested that CYP1A did not produce significant levels of DNA-reactive metabolites from BaP. The protective effects of CYP1A in Elizabeth River sediment extract (ERSE)-exposed nematodes were less pronounced than those seen in BaP-exposed nematodes; CYP1A expression protected against ERSE-induced reduction of steady-state ATP levels, but not other outcomes of exposure to sediment extracts. Overall, we find that in C. elegans, a basal level of CYP1A activity is protective against the examined PAH exposures.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping