Studies of early hepatocellular proliferation and peroxisomal proliferation in Wistar rats treated with herbicide diclofop.
A study was performed to determine whether diclofop (2-(4-(2,4-dichlorophenoxy) phenoxy)propionic acid), introduced as a herbicide, exhibits the properties of peroxisome proliferators (PPs). Diclofop was administered orally at 7-56 mg/kg body weight per day to male Wistar rats for 2, 4, 7 or 14 consecutive days and some effects regarded as early hepatic markers of PPs were studied. The early changes in rat liver, produced by short-term treatment with diclofop consisted of mitogenesis and, time- and dose-related increase in liver weight. Hepatomegaly was typically associated with proliferation of smooth endoplasmic reticulum (SER) and peroxisomes. The parallel biochemical measurements showed that there was a dose-dependent increase in peroxisomal palmitoyl-CoA oxidation and catalase activity in treated rats. Markers of hepatocellular proliferation (S- and M-phase) indicated that mitogenesis was transient and declined despite continuation of diclofop treatment. The threshold exposure level for the palmitoyl-CoA oxidation (one of the peroxisome proliferation markers) was approximately the same (14 mg/kg body weightxper day) as for the stimulation of mitogenesis in Wistar rats. However, for hepatomegaly and catalase activity the threshold exposure level was 7 mg/kg body weightxper day. The results presented here demonstrate clearly that diclofop belongs to a class of rodent PPs.
Palut
D
D
Department of Environmental Toxicology, National Institute of Hygiene, Chocimska 24, 00-791, Warsaw, Poland.
Ludwicki
J K
JK
Kostka
G
G
Kopec-Szlezak
J
J
Wiadrowska
B
B
Lembowicz
K
K
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000032:analysis; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D055768:Halogenated Diphenyl Ethers; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D006529:Hepatomegaly / Q000139:chemically induced; D006540:Herbicides / Q000494:pharmacology* / Q000633:toxicity; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008854:Microscopy, Electron; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D020025:Peroxisome Proliferators / Q000494:pharmacology* / Q000633:toxicity; D020675:Peroxisomes / Q000187:drug effects / Q000201:enzymology; D010647:Phenyl Ethers / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium
D055768:Halogenated Diphenyl Ethers; D006540:Herbicides; D020025:Peroxisome Proliferators; D010647:Phenyl Ethers; D014316:Tritium; D010171:Palmitoyl Coenzyme A; D004247:DNA; C012891:dichlorfop-methyl; D002374:Catalase; D013936:Thymidine