Low Doses of Neutrons Induce Changes in Gene Expression

Studies were designed to identify genes induced in fibroblasts after exposure to low-dose neutron radiation but not after γ rays. Our past work had shown similar modulation of transcripts for α-tubulin, β- and γ-actins, ornithine decarboxylase and interleukin 1 after exposure to either neutrons or γ rays. However, differences in the expression of β-protein kinase C and c-fos genes were observed, with both being induced after exposure to γ rays but not neutrons. Recently we have identified two genes that are induced after exposure to neutrons but not γ rays: Rp-8 (a gene associated with apoptosis) and the long terminal repeat (LTR) of the human immunodeficiency virus (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 as 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 transfected construct of the chloramphenicol acetyl transferase (CAT) gene driven by the HIV-LTR promoter. Measurements of CAT activity and CAT transcripts after irradiation demonstrated an unresponsiveness to γ rays 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 low-dose-rate neutron irradiation. These results are interesting in light of reports that Rp-8 is induced during apoptosis and that HIV causes apoptosis.