LOW-DOSES OF NEUTRONS INDUCE CHANGES IN GENE-EXPRESSION

Studies were designed to identify genes induced in fibroblasts after e xposure to law-dose neutron radiation but not after gamma rays. Our pa st work had shown similar modulation of transcripts for alpha-tubulin, beta- and gamma-actins, ornithine decarboxylase and interleukin 1 aft er exposure to either neutrons or gamma rays. However, differences in the expression of beta-protein kinase C and c-fos genes were observed, with both being induced after exposure to gamma rays but not neutrons . Recently we have identified two genes that are induced after exposur e to neutrons but not gamma rays: Rp-8 (a gene associated with apoptos is) and the long terminal repeat (LTR) of the human immunodeficiency v irus (HIV). Induction of Rp-8 mRNA was demonstrated in Syrian hamster embryo (SHE) fibroblasts and was found to be induced in cells exposed to neutrons administered at low(0.005 Gy/min) and high dose rate (0.12 Gy/min). No induction of other genes associated with apoptosis such a s Rp-2, bcl-2 and Tcl-30 was observed. The induction of transcription from the LTR of HIV was demonstrated in HeLa cells bearing a transfect ed construct of the chloramphenicol acetyl transferase (CAT) gene driv en by the HIV-LTR promoter. Measurements of CAT activity and CAT trans cripts after irradiation demonstrated an unresponsiveness to gamma ray s over a broad range of doses (0.1-3 Gy). Twofold induction of the HIV -LTR was detected after exposure to neutrons (0.48 Gy) administered at low (0.05 Gy/min) but not high (0.12 Gy/min) dose rates. Ultraviolet- mediated HIV-LTR induction, however, was inhibited by exposure to few- dose-rate neutron irradiation. These results are interesting in light of reports that Rp-8 is induced during apoptosis and that HIV causes a poptosis.