Abstract
Aberrant methylation of CpG islands, which are CpG dinucleotide rich areas located in the promoter region of many genes, serves as a mechanism for inactivation of tumor suppressor genes in many cancers. Recently, it is reported that lung tumors induced by plutonium and, to a lesser extent, X-rays showed higher frequency of estrogen receptor (ER) promoter than those induced by NNK, suggesting a close link between radiation exposure and promoter methylation. Recently we found 5' flanking region of membranous amino acid transporter gene, Slc7a10, was heavily methylated in MNU-induced rat mammary tumors (The 48th JRRS meeting, Hiroshima). Slc family is suspected as a new tumor suppressor gene in human colon and breast cancers. In the present study, we examined the status of expression and promoter methylation of Slc family genes in radiation (gamma-rays or carbon ions) -induced rat mammary tumors comparing with spontaneous and chemically (MNU or PhIP) induced ones.
It was found that promoter of Slc7a10 was heavily methylated in chemically induced tumors, but less methylated in spontaneous and radiation-induced ones. It suggested that promoter methylation of Slc7a10 is dependent on the carcinogens in rat mammary tumors. Other Slc genes, which contain CpG islands in promoter, are now under investigation.
