Methylation of SOCS3 and p15 in carbon-ion-induced thymic lymphomas of B6C3F1 mice

Transcriptional suppression of genes by promoter hypermethylation is an important mechanism of inactivation of tumor suppressor genes. The aim of this study was to elucidate the distribution of methylation pattern of the genes, p15 and Socs3, which are involved in proliferation of T-lymphocytes, in mouse thymic lymphomas (TLs) induced by high LET-carbon-ions. TLs were induced by carbon-ion irradiation with spread-out Bragg peak with LET of 40-90 keV/um (HIMAC in Chiba) of five-old-female B6C3F1 mice once a week for 4 consecutive weeks. Distrubution of methylation was determined by bisulfite treatment followed by sequence analysis. It was found that p15 was not methylated in normal thymocytes, while it was methykated in 30% of TL cells. The frequency of methylation and expression of p15 showed inverse correlation. Methylation pattern of Socs3 in normal thymocytes exhibited high methylation in the 3\u27-region from starting codon. Methylation status of Socs3 in TLs was heterogeous; some TLs showed dense methylatioin throughout promoter region, while the other TLs showed hypo-methylation. The correlation of methylation pattern and expression pattern was not observed. These results suggest that methylation status differes among genes in TLs, and that it does not always correlate the expression.13th International Congress of Radiation Researc