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Effect of diphenyl ether herbicides and oxadiazon on porphyrin biosynthesis in mouse liver, rat primary hepatocyte culture and HepG2 cells

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Abstract

The effects of the herbicides fomesafen, oxyfluorfen, oxadiazon and fluazifop-butyl on porphyrin accumulation in mouse liver, rat primary hepatocyte culture and HepG2 cells were investigated. Ten days of herbicide feeding (0.25% in the diet) increased the liver porphyrins in male C57B1/6J mice from 1.4±0.6 to 4.8±2.1 (fomesafen) 16.9±2.9 (oxyfluorfen) and 25.9±3.1 (oxadiazon) nmol/g wet weight, respectively. Fluazifop-butyl had no effect on liver porphyrin metabolism. Fomesafen, oxyfluorfen and oxadiazon increased the cellular porphyrin content of rat hepatocytes after 24 h of incubation (control, 3.2 pmol/mg protein, fomesafen, oxyfluorfen and oxadiazon at 0.125 mM concentration 51.5, 54.3 and 44.0 pmol/mg protein, respectively). The porphyrin content of HepG2 cells increased from 1.6 to 18.2, 10.6 and 9.2 pmol/mg protein after 24 h incubation with the three herbicides. Fluazifop-butyl increased hepatic cytochrome P450 levels and ethoxy- and pentoxyresorufin O-dealkylase (EROD and PROD) activity, oxyfluorfen increased PROD activity. Peroxisomal palmitoyl CoA oxidation increased after fomesafen and fluazifop treatment to about 500% of control values both in mouse liver and rat hepatocytes. Both rat hepatocytes and HepG2 cells can be used as a test system for the porphyrogenic potential of photobleaching herbicides.

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Authors and Affiliations

  1. Research Institute of Toxicology, University of Utrecht, POB 80.176, NL-3508, TD Utrecht, The Netherlands

    Ineke van Holsteijn, Ine Hassing & Bas J. Blaauboer

  2. Department of Pathological Physiology, First Medical Faculty, Charles University, U nemocnice 5, CZ-12853, Prague, Czech Republic

    Jan Krijt & Martin Vokurka

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  1. Jan Krijt
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  2. Ineke van Holsteijn
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  3. Ine Hassing
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  4. Martin Vokurka
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  5. Bas J. Blaauboer
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Krijt, J., van Holsteijn, I., Hassing, I. et al. Effect of diphenyl ether herbicides and oxadiazon on porphyrin biosynthesis in mouse liver, rat primary hepatocyte culture and HepG2 cells. Arch Toxicol 67, 255–261 (1993). https://doi.org/10.1007/BF01974344

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  • DOI: https://doi.org/10.1007/BF01974344

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