Superiority of rat over murine model for studies on the evolution of cancer genome. (2nd December 2018)

• Record Type: Journal Article
• Authors: Akatsuka, Shinya; Li, Guang Hua; Toyokuni, Shinya
• Is Part Of: Free radical research. Volume 52:Number 11/12(2018)
• Page Start: 1323
• Page End: 1327
• Publication Date: 2018-12-02
• Subjects: Renal cell carcinoma -- oxidative stress -- iron -- array-based comparative genome hybridisation -- evolution; Free radicals (Chemistry) -- Periodicals; Antioxidants -- Periodicals; Vitamin C -- Periodicals; Vitamin E -- Periodicals; 541.224
• DOI: 10.1080/10715762.2018.1467562
• Languages: English
• ISSNs: 1071-5762

Abstract

Abstract: Evolution of the species and carcinogenesis are similar in that genomic alterations are the key events. Oxidative stress derived from various etiologies is one of the major causes of carcinogenesis by inducing mutations in the genome. Persistent oxidative stress in the renal proximal tubules through Fenton reaction catalysed by ferric nitrilotriacetate (Fe-NTA) generates renal cell carcinoma (RCC) in mice and rats. Here, in order to observe the species difference in oxidative stress-induced carcinogenesis and to obtain an insight regarding the characteristics of each species, we compared the genomic alterations using array-based comparative genome hybridisation among RCCs in Mutyh knockout/wild-type mice ( C57BL/6 background) induced by Fe-NTA, RCCs in F1 hybrids of Brown-Norway/Fischer-344 wild-type rats and clear cell renal cell carcinoma (CCRCC)/papillary renal cell carcinoma (PRCC) of humans. The average deviated fraction of genomic segments, either loss or gain, from the standard biallelic position was 0.220 ( N = 4), 0.304 ( N = 11), 0.283 ( N = 12), and 0.261 ( N = 5), respectively, for murine RCC, rat RCC, human CCRCC, and human PRCC. Notably, gain/loss ratio was remarkably different as indicated by 0.0820, 0.161, 0.821, and 4.44, respectively. These data suggest that higher species require more genomic alterations with amplification preference for renal carcinogenesis. Further studies are necessary to identify the molecular mechanisms whether the present results depend on cellular functional differences, etiology of carcinogenesis or the target cells in carcinogenesis.