caa a22 4500 445852852 CHVBK 20180317145418.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s00204-010-0640-7 doi (NATIONALLICENCE)springer-10.1007/s00204-010-0640-7 Relationship between CYP1A induction by indole-3-carbinol or flutamide and liver tumor-promoting potential in rats [Elektronische Daten] [Keisuke Shimamoto, Yasuaki Dewa, Sayaka Kemmochi, Eriko Taniai, Hitomi Hayashi, Masako Imaoka, Makoto Shibutani, Kunitoshi Mitsumori] To investigate liver tumor-promoting potentials of indole-3-carbinol (I3C) and flutamide (FLU), changes in mRNA expression of Cyp1a and genes encoding antioxidant/detoxifying enzymes in the liver, 6-week-old male F344 rats were subjected to medium-term liver bioassay. β-Naphthoflavone (BNF), a strong CYP1A inducer, was also used for comparison. Two weeks after initiation with N-diethylnitrosamine (DEN), animals were fed a basal diet (untreated controls) or a diet containing 0.5% I3C, 0.1% FLU, or 0.5% BNF for 6weeks. Each animal was subjected to a two-third partial hepatectomy 1week after the start of promoter treatments. Histopathologically, I3C and BNF increased altered liver cell foci with the incidence (3.7- and 7.3-fold) and multiplicity (8.3- and 13.8-fold) compared with the DEN-alone group, respectively. Immunohistochemically, I3C significantly increased the number (3.1-fold; P<0.01) and area (2.4-fold; P<0.05) of foci positive for glutathione-S-transferase placental form (GST-P) compared with the DEN-alone group; FLU induced a slight but significant increase in the number of GST-P-positive foci (2.8-fold; P<0.05) whereas BNF showed marked induction of the number and area of GST-P-positive foci (20- and 14-fold, respectively; P<0.01). In parallel, I3C, FLU, and BNF markedly increased mRNA levels of Cyp1a1 (50-, 23-, 299-fold) and antioxidant/detoxifying enzymes such as Gpx2 and Nqo1 as shown by real-time reverse transcription-polymerase chain reaction analysis. These results suggest that I3C and FLU could promote hepatocellular tumors in parallel with that of CYP1A's potential to cause subsequent oxidative stress responses in rats. Springer-Verlag, 2010 CYP1A inducer nationallicence Indole-3-carbinol nationallicence Flutamide nationallicence β-Naphthoflavone nationallicence Tumor promotion nationallicence Hepatocarcinogenesis nationallicence Shimamoto Keisuke Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu-shi, Tokyo, Japan aut Dewa Yasuaki Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu-shi, Tokyo, Japan aut Kemmochi Sayaka Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu-shi, Tokyo, Japan aut Taniai Eriko Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu-shi, Tokyo, Japan aut Hayashi Hitomi Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu-shi, Tokyo, Japan aut Imaoka Masako Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu-shi, Tokyo, Japan aut Shibutani Makoto Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu-shi, Tokyo, Japan aut Mitsumori Kunitoshi Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu-shi, Tokyo, Japan aut Archives of Toxicology Springer-Verlag 85/9(2011-09-01), 1159-1166 0340-5761 85:9<1159 2011 85 204 https://doi.org/10.1007/s00204-010-0640-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0640-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Shimamoto Keisuke Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu-shi, Tokyo, Japan aut NATIONALLICENCE 700 1- Dewa Yasuaki Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu-shi, Tokyo, Japan aut NATIONALLICENCE 700 1- Kemmochi Sayaka Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu-shi, Tokyo, Japan aut NATIONALLICENCE 700 1- Taniai Eriko Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu-shi, 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-shi, Tokyo, Japan aut NATIONALLICENCE 700 1- Imaoka Masako Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, 183-8509, Fuchu-shi, 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-shi, 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-shi, Tokyo, Japan aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/9(2011-09-01), 1159-1166 0340-5761 85:9<1159 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer