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PARENT SESSION

Mutagenesis & Carcinogenesis

Monday, October 17, 2005 1:30 PM-3:00 PM Room No. 603
Chair(s): Giaccia, Amato; Barcellos-Hoff, Mary Helen

(MS035) Comparison of gene expression in rat skin following comparable doses of electron or 56Fe ion radiation.

Burns, Fredric*,1, Zhang, Ronghe1, Chen, Shuaili1, Uddin, Ahmed1, Wu, Feng, 1 Environmental Medicine, New York, NY, USA

ABSTRACT- Radiation-induced biological damage elicits a variety of repair pathways that tend to lessen the amount of damage. Less attention has been paid to what gene expression changes are linked to differing LET values. Electron radiation produces a distinctive pattern of gene expression, largely related to increased oxidative stress and proliferative responses. The purpose of the present work was to survey gene expression patterns in rat skin exposed to a beam of 56Fe ions as a basis for understanding how gene expression patterns depend on LET. Rat skin was exposed to 3.0 Gy of high energy 56Fe ions (a surrogate for space radiation) generated by the alternating gradient synchrotron (AGS) at Brookhaven National Laboratory or to 9.0 Gy of low LET electrons. At either 1 or 7 days after irradiation about 1.0 cm,2 of skin was excised from the dorsal skin of each animal. After extraction and purification the RNA was reverse transcribed to cDNA by using a dT24 primer adjacent to the T7 RNA polymerase promoter region and the SuperScript™ Choice System kit (Gibco BRL, NY). The cDNAs were then transcribed to mRNAs and were differentially displayed by means of the Affymetrix (Santa Clara, CA) rat genome microarray (RAT U34-A). A total of 34 microarray results were processed by BRB ArrayTools and GeneSpring software in a search for significantly altered gene expression. Real time PCR consistently verified the Affymetrix results for a panel of genes, although the real-time fold changes were consistently lower than the Affymetrix values. For 56Fe ion or electon radiation 90 or 232 genes respectively were altered (over 90% by upregulation) by 3.5 fold or more with parametric p-values of 0.001 or less. By 7 days after irradiation all altered expression levels had returned to pre-irradiation levels. Some notable genes altered by the low LET and not or less by the high LET included interleukin 1 beta, cathepsin S, and several proteases and phosphatases. Overall the results indicate the low LET radiation was far more active than the high for inducing inflammatory and/or oxidative stress-related genes. The results help to explain why cancers induced by low LET radiation are more easily prevented by anti-oxidative agents than cancers induced by high LET radiation. Work supported by NASA, NCI and NIEHS.

Key words: LET, gene expression, rat skin, RBE


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2005 RRS