@misc{oai:repo.qst.go.jp:00070520, author = {Nishimura, Mayumi and Imaoka, Tatsuhiko and Takabatake, Takashi and Fukuda, Maki and Daino, Kazuhiro and Kakinuma, Shizuko and Takabatake, Masaru and Shimada, Yoshiya and 西村 まゆみ and 今岡 達彦 and 高畠 貴志 and 福田 真希 and 臺野 和広 and 柿沼 志津子 and 高畠 賢 and 島田 義也}, month = {Sep}, note = {Background: Epidemiological studies indicate that breast is one of the most susceptible organs to radiation-induced carcinogenesis. Most studies, however, have failed in identifying clear genetic alterations in radiation-induced breast/mammary cancers. We therefore aimed at identifying genomic changes in the radiation-induced rat mammary cancers. Experimental procedures: F1 hybrid rats were generated by crossing mammary cancer susceptible Sprague-Dawley females with resistant Copenhagen males. They were exposed to 4 Gy gamma-rays at 7 weeks of age and underwent autopsy at the time of spontaneous death. Genome-wide DNA copy number was analyzed by array comparative genomic hybridization. Loss of heterozygosity (LOH) and quantitative RT-PCR analyses were also performed. Results: Copy number losses were identified in small regions of chromosomes 1q52, 2q12-15 and 3q31-36. These correspond to the syntenic regions of human chromosomes, 10q23, 5q11.2 and 11p13-14, respectively, where genomic loci is frequently reported to be deleted. LOH was observed frequently in chromosomes 1 and 2; the loss was either paternal or maternal depending on the chromosome. The lost region of chromosomes 1-3 contained breast cancer-related genes such as Pten, Pik3r1, Fas, Map3k1, Wt1, Il6st, Rad51, Bcl2l11 and Tp53bp1. Among these genes, expression of Fas and Il6st was significantly lower than that in the normal mammary gland. Conclusions: The loss of above chromosomal regions may be causative in radiation induction of rat mammary carcinoma through abrogation of apoptosis and interleukin 6 pathways., 14th International Congress of Radiation Research}, title = {Loss of heterozygosity and copy number changes in the genome of radiation-induced mammary carcinoma of (Sprague-Dawley x Copenhagen) F1 hybrid rats}, year = {2011} }