Absence of in vivo genotoxicity and liver initiation activity of dicyclanil.
In order to clarify the in vivo genotoxicity of dicyclanil with the potential of hepatocarcinogenicity, the stomach, colon, liver, kidney, urinary bladder, lung, brain and bone marrow of male ddY mice given a single oral administration of 100 and 200 mg/kg body weight of dicyclanil were evaluated in an alkaline single-cell gel electrophoresis (comet) assay. In addition, to investigate its possible initiation activity, partially hepatectomized male F344 rats given a single oral administration of 75 mg/kg body weight of dicyclanil were examined by a short-term liver initiation assay. Three and 24 hr after administration, cell migration, as a marker of DNA damage in comet assay, was not observed in any of the tissues of dicyclanil-treated mice. There were no significant differences in the number and area of glutathione S-transferase placental form (GST-P) positive foci, as a marker of hepatocellular preneoplastic lesions in rats, between treated and control groups. These results indicate that dicyclanil has neither in vivo genotoxicity nor initiation activity, and suggest that the hepatocarcinogenicity in mice induced by dicyclanil is attributable to a non-genotoxic mechanism.
Moto
Mitsuyoshi
M
Laboratory of Veterinary Pathology, University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo 183-8509, Japan.
Sasaki
Yu F
YF
Okamura
Miwa
M
Fujita
Miho
M
Kashida
Yoko
Y
Machida
Noboru
N
Mitsumori
Kunitoshi
K
D000284:Administration, Oral; D000818:Animals; D002251:Carbon Tetrachloride / Q000494:pharmacology; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D020552:Comet Assay; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000378:metabolism; D006498:Hepatectomy; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007605:Juvenile Hormones / Q000008:administration & dosage / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology
D002273:Carcinogens; D007605:Juvenile Hormones; D009153:Mutagens; D002251:Carbon Tetrachloride; C121718:dicyclanil; D005982:Glutathione Transferase