Journal Article Fenton reaction-induced renal carcinogenesis in Mutyh-deficient mice exhibits less chromosomal aberrations than the rat model

Li, Guang Hua  ,  Akatsuka, Shinya  ,  Chew, Shan Hwu  ,  Jiang, Li  ,  Nishiyama, Takahiro  ,  Sakamoto, Akihiko  ,  Takahashi, Takashi  ,  Futakuchi, Mitsuru  ,  Suzuki, Hiromu  ,  Sakumi, Kunihiko  ,  Nakabeppu, Yusaku  ,  Toyokuni, Shinya

67 ( 11 )  , pp.564 - 574 , 2017-11 , Wiley
ISSN:1320-5463
Description
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 (P = 0.157) 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.
Full-Text

https://nagoya.repo.nii.ac.jp/?action=repository_action_common_download&item_id=25091&item_no=1&attribute_id=17&file_no=1

Number of accesses :  

Other information