著者

Ken YAMAGUCHI Kenichi URAKAMI Takeshi NAGASHIMA Yuji SHIMODA Shumpei OHNAMI Sumiko OHNAMI Keiichi OHSHIMA Tohru MOCHIZUKI Keiichi HATAKEYAMA Masakuni SERIZAWA Yasuto AKIYAMA Kouji MARUYAMA Hirohisa KATAGIRI Yuji ISHIDA Kaoru TAKAHASHI Seiichiro NISHIMURA Masanori TERASHIMA Taiichi KAWAMURA Yusuke KINUGASA Yushi YAMAKAWA Tetsuro ONITSUKA Yasuhisa OHDE Takashi SUGINO Ichiro ITO Hiroyuki MATSUBAYASHI Yasue HORIUCHI Maki MIZUGUCHI Mutsumi YAMAZAKI Kengo INOUE Kimiko WAKAMATSU Misato SUGIYAMA Katsuhiko UESAKA Masatoshi KUSUHARA

出版者

バイオメディカルリサーチプレス

雑誌

Biomedical Research (ISSN:03886107)

巻号頁・発行日

vol.37, no.4, pp.259-264, 2016-08-01 (Released:2016-08-20)

参考文献数

25

被引用文献数

7

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Using whole exome sequencing data obtained from 1,685 Japanese cancer patients, we examined genetic variations of germline TP53 and found 10 types of non-synonymous single nucleotide variants. In the present study, we focused on 6 patients with germline D49H mutation located in the transactivation domain 2 of p53 protein, since the mutation seemed to be prevalent in cancer patients and to be pathogenic. According to the initial survey for family history of the proband with the germline TP53 D49H mutation, one osteosarcoma patient and his pedigree fulfill the criteria for Li-Fraumeni-like syndrome and the 2009 Chompret criteria for germline TP53 mutation screening. Since this patient possesses double germline mutations of TP53 D49H and A159D, further studies are required to evaluate contribution of the D49H mutation in this morbidity. The remaining 5 patients had family histories of cancer, but none fulfills the criteria either for the Li-Fraumeni/Li-Fraumeni-like syndromes or the 2009 Chompret criteria for germline TP53 mutation screening. It is possible to postulate that the germline TP53 D49H mutation is likely to be low-penetrant in some pedigrees. The present study also indicates that the survey for the germline TP53 mutation plays an important role in clinical practice as it will prevent mistaking cancer patients with unusual heredities for sporadic cases.

著者

Masako Ichikawa Norio Kato Erika Toda Masakazu Kashihara Yuji Ishida Yukoh Hiei Sachiko N. Isobe Kenta Shirasawa Hideki Hirakawa Takashi Okamoto Toshihiko Komari

出版者

Japanese Society of Breeding

雑誌

Breeding Science (ISSN:13447610)

巻号頁・発行日

vol.73, no.3, pp.349-353, 2023 (Released:2023-07-27)

参考文献数

25

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Somaclonal variation was studied by whole-genome sequencing in rice plants (Oryza sativa L., ‘Nipponbare’) regenerated from the zygotes, mature embryos, and immature embryos of a single mother plant. The mother plant and its seed-propagated progeny were also sequenced. A total of 338 variants of the mother plant sequence were detected in the progeny, and mean values ranged from 9.0 of the seed-propagated plants to 37.4 of regenerants from mature embryos. The natural mutation rate of 1.2 × 10–8 calculated using the variants in the seed-propagated plants was consistent with the values reported previously. The ratio of single nucleotide variants (SNVs) among the variants in the seed-propagated plants was 91.1%, which is higher than 56.1% previously reported, and not significantly different from those in the regenerants. Overall, the ratio of transitions to transversions of SNVs was lower in the regenerants as shown previously. Plants regenerated from mature embryos had significantly more variants than different progeny types. Therefore, using zygotes and immature embryos can reduce somaclonal variation during the genetic manipulation of rice.

著者

Koya Sato Seigo Sanoh Yuji Ishida Chise Tateno Shigeru Ohta Yaichiro Kotake

出版者

The Japanese Society of Toxicology

雑誌

The Journal of Toxicological Sciences (ISSN:03881350)

巻号頁・発行日

vol.47, no.7, pp.277-288, 2022 (Released:2022-07-01)

参考文献数

40

被引用文献数

3

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Felbamate (FBM) is an antiepileptic drug that has minimal toxicity in preclinical toxicological species but has a serious idiosyncratic drug toxicity (IDT) in humans. The formation of reactive metabolites is common among most drugs associated with IDT, and 2-phenylpropenal (2-PP) is believed to be the cause of IDT by FBM. It is important to consider the species difference in susceptibility to IDT between experimental animals and humans. In the present study, we used an in vitro and in vivo model system to reveal species difference in IDT of FBM. Human cytochrome P450 (CYP) and carboxylesterase (CES) expressing microsomes were used to clarify the isozymes involved in the metabolism of FBM. The remaining amount of FBM was significantly reduced in incubation with microsomes expressing human CYP2C8, 2C9, 2E1, and CES1c isozymes. Chimeric mice with humanized liver are expected to predict IDT in humans. Therefore, metabolite profiles in chimeric mice with humanized liver were investigated after administration of FBM. Metabolites after glutathione (GSH) conjugation of 2-phenylpropenal (2-PP), which is the reactive metabolite responsible for FBM-induced IDT, were detected in chimeric mice plasma and liver homogenate. Mass spectrometry imaging (MSI) visualizes distribution of FBM and endogenous GSH, and GSH levels in human hepatocyte were decreased after administration of FBM. In this study, we identified CYP and CES isozymes involved in the metabolism of FBM and confirmed reactive metabolite formation and subsequent decrease in GSH using humanized animal model. These results would provide useful information for the susceptibility to IDT between experimental animals and humans.