Meyer Joel N.
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PreprintCaenorhabditis elegans generates biologically relevant levels of genotoxic metabolites from aflatoxin B1 but not benzo[a]pyrene in vivo( 2010-08-25) Leung, Maxwell C. K. ; Goldstone, Jared V. ; Boyd, Windy A. ; Freedman, Jonathan H. ; Meyer, Joel N.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 B1 (AFB1), 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 AFB1 and BaP were compared in nucleotide excision repair-deficient (xpa-1) and - proficient (N2) strains of C. elegans. Exposure to AFB1 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-NADPH reductase- deficient strain (emb-8) of C. elegans was found to be more resistant to the growth inhibitory effect of AFB1 exposure than N2, confirming that the AFB1- 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.
PreprintFundulus as the premier teleost model in environmental biology : opportunities for new insights using genomics( 2007-09-01) Burnett, Karen G. ; Bain, Lisa J. ; Baldwin, William S. ; Callard, Gloria V. ; Cohen, Sarah ; Di Giulio, Richard T. ; Evans, David H. ; Gomez-Chiarri, Marta ; Hahn, Mark E. ; Hoover, Cindi A. ; Karchner, Sibel I. ; Katoh, Fumi ; MacLatchy, Deborah L. ; Marshall, William S. ; Meyer, Joel N. ; Nacci, Diane E. ; Oleksiak, Marjorie F. ; Rees, Bernard B. ; Singer, Thomas D. ; Stegeman, John J. ; Towle, David W. ; Van Veld, Peter A. ; Vogelbein, Wolfgang K. ; Whitehead, Andrew ; Winn, Richard N. ; Crawford, Douglas L.A strong foundation of basic and applied research documents that the estuarine fish Fundulus heteroclitus and related species are unique laboratory and field models for understanding how individuals and populations interact with their environment. In this paper we summarize an extensive body of work examining the adaptive responses of Fundulus species to environmental conditions, and describe how this research has contributed importantly to our understanding of physiology, gene regulation, toxicology, and ecological and evolutionary genetics of teleosts and other vertebrates. These explorations have reached a critical juncture at which advancement is hindered by the lack of genomic resources for these species. We suggest that a more complete genomics toolbox for F. heteroclitus and related species will permit researchers to exploit the power of this model organism to rapidly advance our understanding of fundamental biological and pathological mechanisms among vertebrates, as well as ecological strategies and evolutionary processes common to all living organisms.