caa a22 4500 445853735 CHVBK 20180317145421.0 cr unu---uuuuu 170323e20110801xx s 000 0 eng 10.1007/s00204-010-0628-3 doi (NATIONALLICENCE)springer-10.1007/s00204-010-0628-3 Evaluation of in vivo genotoxic potential of fenofibrate in rats subjected to two-week repeated oral administration [Elektronische Daten] [Mohammad Tawfeeq, Terumasa Suzuki, Keisuke Shimamoto, Hitomi Hayashi, Makoto Shibutani, Kunitoshi Mitsumori] Fenofibrate (FF), a peroxisome proliferator-activated receptor-alpha agonist, has been used as one of the hypolipidemic drugs in man and induces oxidative stress and promotes hepatocarcinogenesis in the liver of rodents. This chemical belongs to a class of non-genotoxic carcinogens, but DNA damage secondary to oxidative stress resulting from reactive oxygen species (ROS) generation is suspected in rodents given this chemical. To examine whether FF has genotoxic potential, partially hepatectomized F344 male rats were treated orally with 0, 1,000 or 2,000mg/kg of FF for 2weeks, followed by diet containing 0.15% 2 acetyl aminofluorene (2 AAF) for enhancement the tumor-promoting effect for 10days and a single oral dose of carbon tetrachloride (CCl4) as the first experiment (liver initiation assay). As the second experiment, the in vivo liver comet assay was performed in hepatectomized rats, and the expression of some DNA repair genes was examined. In the liver initiation assay, the number and area of glutathione S-transferase placental form (GST-P)-positive single cells and foci did not increase in the FF treated groups. In the comet assay, positive results were obtained after 3h of the last treatment of FF, and the expression of some DNA repair genes such as Apex1, Ogg1 and Mlh1 were upregulated in rats given the high dose of FF at 3h after the treatment but not in 24h after the treatment. The results of the present study suggest that FF causes some DNA damage in livers of rats, but is not a strong genotoxic substance leading to a DNA mutation since such DNA damage was repaired by the increased activity of some DNA repair genes. Springer-Verlag, 2010 Fenofibrate nationallicence Comet assay nationallicence Initiation assay nationallicence Genotoxicity nationallicence Rat nationallicence Tawfeeq Mohammad Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu, Tokyo, Japan aut Suzuki Terumasa Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu, Tokyo, Japan aut Shimamoto Keisuke Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu, Tokyo, Japan aut Hayashi Hitomi Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu, Tokyo, Japan aut Shibutani Makoto Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu, Tokyo, Japan aut Mitsumori Kunitoshi Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu, Tokyo, Japan aut Archives of Toxicology Springer-Verlag 85/8(2011-08-01), 1003-1011 0340-5761 85:8<1003 2011 85 204 https://doi.org/10.1007/s00204-010-0628-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0628-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Tawfeeq Mohammad Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu, Tokyo, Japan aut NATIONALLICENCE 700 1- Suzuki Terumasa Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu, Tokyo, Japan aut NATIONALLICENCE 700 1- Shimamoto Keisuke Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu, Tokyo, Japan aut NATIONALLICENCE 700 1- Hayashi Hitomi Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu, Tokyo, Japan aut NATIONALLICENCE 700 1- Shibutani Makoto Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu, Tokyo, Japan aut NATIONALLICENCE 700 1- Mitsumori Kunitoshi Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu, Tokyo, Japan aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/8(2011-08-01), 1003-1011 0340-5761 85:8<1003 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer