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Caenorhabditis elegans generates biologically relevant levels of genotoxic metabolites from aflatoxin B1 but not benzo[a]pyrene in vivo

Publication ,  Journal Article
Leung, MCK; Goldstone, JV; Boyd, WA; Freedman, JH; Meyer, JN
Published in: Toxicological Sciences
2010

There is relatively little information regarding the critical xenobiotic-metabolizing cytochrome P450 (CYP) enzymes in Caenorhabditis elegans, despite this organism's increasing use as a model in toxicology and pharmacology. We carried out experiments to elucidate the capacity of C. elegans to metabolically activate important promutagens via CYPs. Phylogenetic comparisons confirmed an earlier report indicating a lack of CYP1 family enzymes in C. elegans. Exposure to aflatoxin B(1) (AFB(1)), which is metabolized in mammals by CYP1, CYP2, and CYP3 family enzymes, resulted in significant DNA damage in C. elegans. However, exposure to benzo[a]pyrene (BaP), which is metabolized in mammals by CYP1 family enzymes only, produced no detectable damage. To further test whether BaP exposure caused DNA damage, the toxicities of AFB(1) and BaP were compared in nucleotide excision repair (NER)-deficient (xpa-1) and NER-proficient (N2) strains of C. elegans. Exposure to AFB(1) inhibited growth more in xpa-1 than N2 nematodes, but the growth-inhibitory effects of BaP were indistinguishable in the two strains. Finally, a CYP-nicotinamide adenine dinucleotide phosphate reductase-deficient strain (emb-8) of C. elegans was found to be more resistant to the growth-inhibitory effect of AFB(1) exposure than N2, confirming that the AFB(1)-mediated growth inhibition resulted from CYP-mediated metabolism. Together, these results indicate that C. elegans lacks biologically significant CYP1 family-mediated enzymatic metabolism of xenobiotics. Interestingly, we also found that xpa-1 nematodes were slightly more sensitive to chlorpyrifos than were wild type. Our results highlight the importance of considering differences between xenobiotic metabolism in C. elegans and mammals when using this alternative model in pharmaceutical and toxicological research.

Duke Scholars

Published In

Toxicological Sciences

Publication Date

2010

Volume

118

Start / End Page

444 / 453

Related Subject Headings

  • Toxicology
  • Species Specificity
  • Phylogeny
  • Mutagens
  • DNA Repair
  • DNA Damage
  • DNA
  • Cytochrome P-450 Enzyme System
  • Caenorhabditis elegans
  • Biotransformation
 

Citation

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Leung, M. C. K., Goldstone, J. V., Boyd, W. A., Freedman, J. H., & Meyer, J. N. (2010). Caenorhabditis elegans generates biologically relevant levels of genotoxic metabolites from aflatoxin B1 but not benzo[a]pyrene in vivo. Toxicological Sciences, 118, 444–453.
Leung, M. C. K., J. V. Goldstone, W. A. Boyd, J. H. Freedman, and J. N. Meyer. “Caenorhabditis elegans generates biologically relevant levels of genotoxic metabolites from aflatoxin B1 but not benzo[a]pyrene in vivo.” Toxicological Sciences 118 (2010): 444–53.
Leung MCK, Goldstone JV, Boyd WA, Freedman JH, Meyer JN. Caenorhabditis elegans generates biologically relevant levels of genotoxic metabolites from aflatoxin B1 but not benzo[a]pyrene in vivo. Toxicological Sciences. 2010;118:444–53.
Leung MCK, Goldstone JV, Boyd WA, Freedman JH, Meyer JN. Caenorhabditis elegans generates biologically relevant levels of genotoxic metabolites from aflatoxin B1 but not benzo[a]pyrene in vivo. Toxicological Sciences. 2010;118:444–453.

Published In

Toxicological Sciences

Publication Date

2010

Volume

118

Start / End Page

444 / 453

Related Subject Headings

  • Toxicology
  • Species Specificity
  • Phylogeny
  • Mutagens
  • DNA Repair
  • DNA Damage
  • DNA
  • Cytochrome P-450 Enzyme System
  • Caenorhabditis elegans
  • Biotransformation