Effect of diphenyl ether herbicides and oxadiazon on porphyrin biosynthesis in mouse liver, rat primary hepatocyte culture and HepG2 cells.
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- 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.
Krijt
J
J
Research Institute of Toxicology, University of Utrecht, The Netherlands.
van Holsteijn
I
I
Hassing
I
I
Vokurka
M
M
Blaauboer
B J
BJ
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004095:Dihydropyridines / Q000633:toxicity; D055768:Halogenated Diphenyl Ethers; D006540:Herbicides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D010069:Oxadiazoles / Q000633:toxicity*; D010647:Phenyl Ethers / Q000633:toxicity; D011166:Porphyrins / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D004095:Dihydropyridines; D055768:Halogenated Diphenyl Ethers; D006540:Herbicides; D010069:Oxadiazoles; D010647:Phenyl Ethers; D011166:Porphyrins; C016027:oxyfluorofen; C050582:fluazifop; D003577:Cytochrome P-450 Enzyme System; C012466:oxadiazon