Hepatic Gene Expression Changes in Rats Internally Exposed to Radioactive ⁵⁶MnO₂ Particles at Low Doses

We have studied the biological effects of the internal exposure to radioactive manganese-56 dioxide (⁵⁶MnO₂), the major radioisotope dust found in soil after atomic bomb explosions. Our previous study of blood chemistry indicated a possible adverse effect of ⁵⁶MnO₂ on the liver. In the present study, we further examined the effects on the liver by determining changes in hepatic gene expressions. Male Wistar rats were exposed to ⁵⁶MnO₂ particles (three groups with the whole-body doses of 41, 90, and 100 mGy), stable MnO₂ particles, or external ⁶⁰Co γ-rays (2 Gy), and were examined together with the non-treated control group on postexposure day 3 and day 61. No histopathological changes were observed in the liver. The mRNA expression of a p53-related gene, the cyclin-dependent kinase inhibitor 1A, increased in ⁵⁶MnO₂ as well as in γ-ray irradiated groups on postexposure day 3 and day 61. The expression of a stress-responsive gene, nuclear factor κB, was also increased by ⁵⁶MnO₂ and γ-rays on postexposure day 3. However, the expression of cytokine genes (interleukin-6 or chemokine ligand 2) or fibrosis-related TGF-β/Smad genes (Tgfb1, Smad3, or Smad4) was not altered by the exposure. Our data demonstrated that the internal exposure to ⁵⁶MnO₂ particles at less than 0.1 Gy significantly affected the short-term gene expressions in the liver in a similar manner with 2 Gy of external γ-irradiation. These changes may be adaptive responses because no changes occurred in cytokine or TGF-β/Smad gene expressions.