2024-03-28T13:45:08Z
https://nagoya.repo.nii.ac.jp/oai
oai:nagoya.repo.nii.ac.jp:00025091
2023-01-16T04:15:51Z
499:500:501
Fenton reaction-induced renal carcinogenesis in Mutyh-deficient mice exhibits less chromosomal aberrations than the rat model
Li, Guang Hua
74823
Akatsuka, Shinya
74824
Chew, Shan Hwu
74825
Jiang, Li
74826
Nishiyama, Takahiro
74827
Sakamoto, Akihiko
74828
Takahashi, Takashi
74829
Futakuchi, Mitsuru
74830
Suzuki, Hiromu
74831
Sakumi, Kunihiko
74832
Nakabeppu, Yusaku
74833
Toyokuni, Shinya
74834
Oxidative stress including iron excess has been associated with carcinogenesis. The level of 8-oxoguanine, a major oxidatively modified base in DNA, is maintained very low by three distinct enzymes, encoded by OGG1, MUTYH and MTH1. Germline biallelic inactivation of MUTYH represents a familial cancer syndrome called MUTYH-associated polyposis. Here, we used Mutyh-deficient mice to evaluate renal carcinogenesis induced by ferric nitrilotriacetate (Fe-NTA). Although the C57BL/6 background is cancer-resistant, a repeated intraperitoneal administration of Fe-NTA induced a high incidence of renal cell carcinoma (RCC; 26.7%) in Mutyh-deficient mice in comparison to wild-type mice (7.1%). Fe-NTA treatment also induced renal malignant lymphoma, which did not occur without the Fe-NTA treatment in both the genotypes. Renal tumor-free survival after Fe-NTA treatment was marginally different (Pā=ā0.157) between the two genotypes. Array-based comparative genome hybridization analyses revealed, in RCC, the loss of heterozygosity in chromosomes 4 and 12 without p16INK[4]A inactivation; these results were confirmed by a methylation analysis and showed no significant difference between the genotypes. Lymphomas showed a preference for genomic amplifications. Dlk1 inactivation by promoter methylation may be involved in carcinogenesis in both tumors. Fe-NTA-induced murine RCCs revealed significantly less genomic aberrations than those in rats, demonstrating a marked species difference.
journal article
Wiley
2017-11
application/pdf
PATHOLOGY INTERNATIONAL
11
67
564
574
http://doi.org/10.1111/pin.12598
http://hdl.handle.net/2237/27310
1320-5463
https://nagoya.repo.nii.ac.jp/record/25091/files/deposit_1.pdf
eng
https://doi.org/10.1111/pin.12598
This is the peer reviewed version of the following article: [Li, G. H., Akatsuka, S., Chew, S. H., Jiang, L., Nishiyama, T., Sakamoto, A., Takahashi, T., Futakuchi, M., Suzuki, H., Sakumi, K., Nakabeppu, Y. and Toyokuni, S.(2017), Fenton reaction-induced renal carcinogenesis in Mutyh-deficient mice exhibits less chromosomal aberrations than the rat model.PATHOLOGY INTERNATIONAL.,67: 564ā574. doi:10.1111/pin.12598], which has been published in final form at [http://doi.org/10.1111/pin.12598]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.