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Liver preneoplastic changes in mice treated with the herbicide fomesafen

P Stránská

J Sanitraák

Institute of Pathophysiology, First Faculty of Medicine, Charles University, U nemocnice 5, 128 53, Prague, Czech Republic

A Chlumská

F Fakan

Sikl's Department of Pathology, Medical Faculty, Charles University, Pilsen, Czech Republic

1. 1 Effect of the diphenyl ether herbicide fomesafen on liver preneoplastic changes and porphyrin biosynthesis was examined in male C57BL/6J mice (0.23% in the diet for 14 months) and ICR mice (0.3% in the diet for 50 weeks). Fomesafen treatment resulted in preneoplastic changes (liver nodules and foci of altered hepatocytes) in both strains, uroporphyria developed only in ICR mice.
   
2. 2 Iron pretreatment (600 mg/kg as a single dose) accelerated the development of fomesafen-induced preneoplastic changes in both mouse strains. The number of foci containing altered hepatocytes, as well as the number and size of liver nodules, were increased in iron-pretreated animals.
   
3. 3 A single injection of iron induced marked uroporphyria in C57BL/6J mice after 14 months (liver porphyrin content 102 nmol/g). This uroporphyria was further potentiated by fomesafen administration (208 nmol/g).
   
4. 4 In ICR mice, liver histology was apparently normal after a 3 month recovery from fomesafen treatment (0.32% for 9 months). Liver porphyrin content (260 nmol/g) started to decrease immediately after fomesafen withdrawal, but was still significantly elevated after 3 months (5 nmol/g), as compared to controls (1 nmol/g).
   
5. 5 It is concluded that the toxicological evaluation of fomesafen should focus on liver porphyrin biosynthesis.
   

Key Words: fomesafen • herbicides • liver neoplasms • peroxisome proliferation • porphyria • uroporphyrins

Human & Experimental Toxicology, Vol. 18, No. 5, 338-344 (1999)
DOI: 10.1191/096032799678840129


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