Calorie restriction alters the mechanisms of radiation-induced mouse thymic lymphomagenesis

• DOI: 10.1371/journal.pone.0280560
• Publication Date: 2023-01-20T18:50:11Z
• Authors: Takafumi Nakayama; Masaaki Sunaoshi; Yi Shang; Mizuki Takahashi; Takato Saito; Benjamin J. Blyth; Yoshiko Amasaki; Kazuhiro Daino; Yoshiya Shimada; Akira Tachibana; Shizuko Kakinuma
• Keywords: 0301 basic medicine; Neoplasms, Radiation-Induced; Science; Q; R; Loss of Heterozygosity; Thymus Neoplasms; Mice; 03 medical and health sciences; Mutation; Medicine; Animals; Point Mutation; Alleles; Research Article; Caloric Restriction

Calorie restriction (CR) suppresses not only spontaneous but also chemical- and radiation-induced carcinogenesis. Our previous study revealed that the cancer-preventive effect of CR is tissue dependent does effectively prevent development thymic lymphoma (TL). We investigated association between genomic alterations resulting TLs to clarify underlying resistance mechanism. were obtained from new experiments, in which B6C3F1 mice exposed radiation at 1 week age fed with a or standard (non-CR) diet 7 weeks throughout their lifetimes. All available used for analysis DNA. In contrast non-CR group, those group displayed suppression copy-neutral loss heterozygosity (LOH) involving relevant tumor suppressor genes ( Cdkn2a , Ikzf1 Trp53 Pten ), an event regarded as cell division–associated. However, did affect interstitial deletions genes, observed both groups. addition, affected mechanism inactivation TLs: exhibited LOH duplicated inactive alleles, whereas showed expression dominant-negative isoforms accompanying point mutation intragenic deletion. These results suggest that, even though reduces division–related rearrangements by suppressing proliferation, tumors arise via diverse carcinogenic pathways including suppressors other mutations. findings provide molecular basis improved prevention strategies overcome lymphomagenesis.