Gene expression profiles in mouse liver cells after exposure to different types of radiation.

The liver is one of the target organs of radiation-induced cancers by internal exposures. In order to elucidate radiation-induced liver cancers including Thorotrast, we present a new approach to investigate in vivo effects of internal exposure to alpha-particles. Adopting boron neutron capture, we separately irradiated Kupffer cells and endothelial cells in mouse liver in vivo and analyzed the changes in gene transcriptions by an oligonucleotide microarray. Differential expression was defined as more than 3-fold for up-regulation and less than 1/3 for under-regulation, compared with non-irradiated controls. Of 6,050 genes examined, 68 showed differential expression compared with non-irradiated mice. Real-time polymerase chain reaction validated the results of the microarray analysis. Exposure to alpha-particles and gamma-rays produced different patterns of altered gene expression. Gene expression profiles revealed that the liver was in an inflammatory state characterized by up-regulation of positive acute phase protein genes, irrespective of the target cells exposed to radiation. In comparison with chemical and biological hepatotoxicants, inductions of Metallothionein 1 and Hemopexin, and suppressions of cytochrome P450s are characteristic of radiation exposure. Anti-inflammatory treatment could be helpful for the prevention and protection of radiation-induced hepatic injury.