BioProject

Understanding the relationship between radiation-induced breast cancer and obesity, together with information on underlying mechanisms, are potentially useful in risk management and prevention of second cancer in patients receiving radiotherapy. More...

Understanding the relationship between radiation-induced breast cancer and obesity, together with information on underlying mechanisms, are potentially useful in risk management and prevention of second cancer in patients receiving radiotherapy. The present study aims to develop a novel animal model to study the relationship by combining two Sprague-Dawley rat models of radiation carcinogenesis and diet-induced obesity. Mammary carcinomas were induced in female obese and lean rats by irradiation with 4 Gy of gamma rays. Gene expression of mammary carcinomas and normal mammary tissues were analyzed with Agilent Whole Rat Genome DNA microarray. The result indicated that genes related to translation and oxidative phosphorylation were upregulated in carcinomas of obese rats. Overall design: Female Sprague-Dawley (Jcl:SD) rats fed on a high fat diet (45 kcal% fat) were divided into obesity prone (OP, n = 30) and resistant (OR, n = 30) individuals based on the body weight at 7 weeks of age, when they were whole-body irradiated with 4 Gy of Cs-137 gamma rays at 0.5 Gy/min; lean control (LC, n = 30) rats were fed on a standard diet (10 kcal% fat) and irradiated in the same manner; these groups of rats were observed for development of palpable mammary cancer, while kept on the same diet, for 30 weeks. Mammary adenocarcinomas with homogeneous histology without necrosis or marked infiltrating cells were selected for microarray analysis (OP, n = 6; OR, n = 3; LC, n = 3) as well as normal tissues (OP, n = 3; OR, n = 2; LC, n = 3). Microarray analysis was performed as described previously (T. Imaoka, M. Nishimura, D. Iizuka, et al. Mol Carcinog 50, 539-552, 2011). In brief, total RNA was extracted from frozen tissues and cyanine 3-labeled complementary RNA was generated from total RNA and hybridized to DNA microarrays (Whole Rat Genome Microarray Kit, Agilent Technologies, Inc., Santa Clara, CA, USA). Scanned microarray images were processed with the Feature Extraction 10 software (Agilent Technologies), normalized by the Robust Multi-array Average method and analyzed on GeneSpring GX 12 (Agilent Technologies). Less...