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Key Event Title
Accumulation, Highly carboxylated porphyrins
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Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP||Point of Contact||Author Status||OECD Status|
|AHR activation-uroporphyria||KeyEvent||Amani Farhat (send email)||Open for citation & comment||WPHA/WNT Endorsed|
Key Event Description
Under normal conditions, the heme biosynthesis pathway is tightly regulated and porphyrins (other than protoporphyrin) are only present in trace amounts. However, when the regulatory process is disturbed, a variety of porphyrin precursors of heme accumulate in various organs including the liver and urinary and fecal excretion is elevated). The pattern of porphyrin accumulation in chicken and rodents is similar following exposure to a variety of chemicals, and can be used to identify which enzyme in the heme pathway is predominately affected.
How It Is Measured or Detected
Methods that have been previously reviewed and approved by a recognized authority should be included in the Overview section above. All other methods, including those well established in the published literature, should be described here. Consider the following criteria when describing each method: 1. Is the assay fit for purpose? 2. Is the assay directly or indirectly (i.e. a surrogate) related to a key event relevant to the final adverse effect in question? 3. Is the assay repeatable? 4. Is the assay reproducible?
The hepatic and urinary/fecal porphyrin patters can be determined using a high-performance liquid chromatograph equipped with a fluorescence detector. Kennedy et al. describe the method for tissue extraction and porphyrin quantification in detail, which is rapid and highly sensitive.
Domain of Applicability
Elevated porphyrins have been reported in mouse, rat, Japanese quail and chicken liver and in clinical diagnosis of humans. Elevated HCPs (highly carboxylated porphyrins) have been measured in Herring gulls from highly contaminated Great Lakes colonies.
- ↑ 1.0 1.1 Marks, G. S., Powles, J., Lyon, M., McCluskey, S., Sutherland, E., and Zelt, D. (1987). Patterns of porphyrin accumulation in response to xenobiotics. Parallels between results in chick embryo and rodents. Ann. N. Y. Acad. Sci. 514, 113-127.
- ↑ Frank, J., and Poblete-Gutierrez, P. (2010) Porphyria cutanea tarda--when skin meets liver. Best. Pract. Res. Clin Gastroenterol. 24(5), 735-745.
- ↑ Kennedy, S. W., Wigfield, D. C., and Fox, G. A. (1986). Tissue porphyrin pattern determination by high-speed high-performance liquid chromatography. Anal. Biochem. 157 (1), 1-7.
Hahn, M. E., Gasiewicz, T. A., Linko, P., and Goldstein, J. A. (1988). The role of the Ah locus in hexachlorobenzene-induced porphyria. Studies in congenic C57BL/6J mice. Biochem. J. 254(1), 245-254.
Goldstein, J. A., Linko, P., and Bergman, H. (1982). Induction of porphyria in the rat by chronic versus acute exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochem. Pharmacol. 31(8), 1607-1613.
Miranda, C. L., Wang, J. L., Henderson, M. C., Carpenter, H. M., Nakaue, H. S., and Buhler, D. R. (1983). Studies on the porphyrinogenic action of 1,2,4-trichlorobenzene in birds. Toxicology 28(1-2), 83-92.
Kennedy, S. W., and Fox, G. A. (1990). Highly carboxylated porphyrins as a biomarker of polyhalogenated aromatic hydrocarbon exposure in wildlife: Confirmation of their presence in Great Lakes herring gull chicks in the early 1970s and important methodological details. Chemosphere 21(3), 407-415.