caa a22 4500 445292911 CHVBK 20180317142534.0 cr unu---uuuuu 170323e20100501xx s 000 0 eng 10.1007/s11626-009-9269-3 doi (NATIONALLICENCE)springer-10.1007/s11626-009-9269-3 Implication of p16 inactivation in tumorigenic activity of respiratory epithelial cell lines and adenocarcinoma cell line established from plutonium-induced lung tumor in rat [Elektronische Daten] [Yutaka Yamada, Akifumi Nakata, Mitsuaki Yoshida, Yoshiya Shimada, Yoichi Oghiso, Jean-Luc Poncy] To investigate whether p16 inactivation is involved in the development of rat pulmonary tumors, we compared the p16 status and tumorigenicity of cell lines which indicated different p16 status. The tumor cell line (PuD2) was established from lung adenocarcinoma induced in plutonium dioxide-inhaled rat in this study. The virus-immortalized SV40T2 cells, benzo[a]pyrene-induced BP cells, BP-derived BP(P)Tu cells, and gamma ray-transformed RTiv3 cells were utilized as the respiratory epithelial cell lines. A tumorigenicity assay-inoculating cells into nude mice revealed that PuD2, BP, and BP(P)Tu cells were tumorigenic, but SV40T2 and RTiv3 cells were not. Methylation-specific PCR of the p16 promoter region revealed that SV40T2 cells were unmethylated, BP cells displayed heterogeneous methylation, and BP(P)Tu and RTiv3 cells were completely methylated. Methylation-specific PCR and PCR of genomic DNA in the p16 region did not amplify product in PuD2 cells, indicating deletion of p16. Banded karyotypes prepared from PuD2 cells exhibited trisomy of chromosome 4, inversion in chromosome 11, and partial deletion of chromosomes 4 and 5. The demethylating agent 5Aza2dC partially demethylated the p16 promoter region of BP(P)Tu, BP and RTiv3 cells, increasing expression of the p16 transcript and decreasing growth of the cells. These results indicate that hypermethylation of the p16 promoter region occurs early in neoplastic transformation before acquisition of tumorigenicity in rat respiratory epithelium. Loss of genes located on chromosomes 4 and 5 may be important for tumor progression and acquisition of high tumorigenic activity in the Pu-induced rat lung tumor. The Society for In Vitro Biology, 2010 Tumor suppressor gene nationallicence Methylation nationallicence Chromosome aberration nationallicence Alpha emitter nationallicence p53 nationallicence Nude mouse nationallicence Yamada Yutaka Experimental Radiobiology for Children's Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, 263-8555, Chiba, Japan aut Nakata Akifumi Experimental Radiobiology for Children's Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, 263-8555, Chiba, Japan aut Yoshida Mitsuaki Department of Radiation Dosimetry, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, 263-8555, Chiba, Japan aut Shimada Yoshiya Experimental Radiobiology for Children's Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, 263-8555, Chiba, Japan aut Oghiso Yoichi Department of Radiobiology, Institute for Environmental Sciences, 1-7, Ienomae, Obuchi, Rokkasho-mura, Kamikita-gun, 039-3212, Aomori, Japan aut Poncy Jean-Luc Départment de Radiobiologie et de Radiopathologie, Laboratoire de Radiotoxicologie, CEA-Direction des Sciences du Vivant, BP 12 91680, Bruyères-le-Châtel, France aut In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 46/5(2010-05-01), 477-486 1071-2690 46:5<477 2010 46 11626 https://doi.org/10.1007/s11626-009-9269-3 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11626-009-9269-3 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yamada Yutaka Experimental Radiobiology for Children's Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, 263-8555, Chiba, Japan aut NATIONALLICENCE 700 1- Nakata Akifumi Experimental Radiobiology for Children's Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, 263-8555, Chiba, Japan aut NATIONALLICENCE 700 1- Yoshida Mitsuaki Department of Radiation Dosimetry, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, 263-8555, Chiba, Japan aut NATIONALLICENCE 700 1- Shimada Yoshiya Experimental Radiobiology for Children's Health Research Group, Research Center for Radiation Protection, National Institute of Radiological Sciences, Anagawa 4-9-1, Inage-ku, 263-8555, Chiba, Japan aut NATIONALLICENCE 700 1- Oghiso Yoichi Department of Radiobiology, Institute for Environmental Sciences, 1-7, Ienomae, Obuchi, Rokkasho-mura, Kamikita-gun, 039-3212, Aomori, Japan aut NATIONALLICENCE 700 1- Poncy Jean-Luc Départment de Radiobiologie et de Radiopathologie, Laboratoire de Radiotoxicologie, CEA-Direction des Sciences du Vivant, BP 12 91680, Bruyères-le-Châtel, France aut NATIONALLICENCE 773 0- In Vitro Cellular & Developmental Biology - Animal Springer-Verlag 46/5(2010-05-01), 477-486 1071-2690 46:5<477 2010 46 11626 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer