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Low-Dose Trichloroethylene Alters Cytochrome P450-2C Subfamily Expression in the Developing Chick Heart

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Abstract

Trichloroethylene (TCE) is an organic solvent and common environmental contaminant. TCE exposure is associated with heart defects in humans and animal models. Primary metabolism of TCE in adult rodent models is by specific hepatic cytochrome P450 enzymes (Lash et al. in Environ Health Perspect 108:177–200, 2000). As association of TCE exposure with cardiac defects is in exposed embryos prior to normal liver development, we investigated metabolism of TCE in the early embryo. Developing chick embryos were dosed in ovo with environmentally relevant doses of TCE (8 and 800 ppb) and RNA was extracted from cardiac and extra-cardiac tissue (whole embryo without heart). Real-time PCR showed upregulation of CYP2H1 transcripts in response to TCE exposure in the heart. No detectable cytochrome expression was found in extra-cardiac tissue. As seen previously, the dose response was non-monotonic and 8 ppb elicited stronger upregulation than 800 ppb. Immunostaining for CYP2C subfamily expression confirmed protein expression and showed localization in both myocardium and endothelium. TCE exposure increased protein expression in both tissues. These data demonstrate that the earliest embryonic expression of phase I detoxification enzymes is in the developing heart. Expression of these CYPs is likely to be relevant to the susceptibility of the developing heart to environmental teratogens.

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Acknowledgments

We would like to thank Dr. André L. Tavares for his guidance and support. This work was supported by the American Heart Association [0810020Z to O.M.] and the National Institutes of Health [HL82851 to R.B.R. and ES00694 to the Southwest Environmental Health Sciences Center (SWEHSC)].

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Authors and Affiliations

  1. Department of Cell Biology and Anatomy, University of Arizona, 1501 N Campbell Avenue, LSN 456, PO Box 245044, Tucson, AZ, 85724-5044, USA

    Om Makwana, Lauren Ahles, Alejandro Lencinas, Ornella I. Selmin & Raymond B. Runyan

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  1. Om Makwana
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  2. Lauren Ahles
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  3. Alejandro Lencinas
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  4. Ornella I. Selmin
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  5. Raymond B. Runyan
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Correspondence to Raymond B. Runyan.

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Makwana, O., Ahles, L., Lencinas, A. et al. Low-Dose Trichloroethylene Alters Cytochrome P450-2C Subfamily Expression in the Developing Chick Heart. Cardiovasc Toxicol 13, 77–84 (2013). https://doi.org/10.1007/s12012-012-9180-0

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