Effects of Simulated Nuclear Fuel Particles on the Histopathology and CYP Enzymes in the Rat Lung and Liver

We studied both short-term (3 and 30 days) and long-term (3-24 months) effects of simulated nuclear fuel particles (neutron-activated UO2) on the rat lung and liver histopathology and cytochrome P450 (CYP) activities. In the short-term study, after a single intratracheal instillation with neutron-activated particles (administered activity 36 kBq), the lung histology revealed inflammation and a decrease in several lung testosterone hydroxylation levels. Liver exhibited normal histology but hepatic testosterone 7 α-hydroxylase (T7αOH) was decreased by 30% at 3 days treatment with neutron-activated particles (9.3 kBq). At 30 days after treatment, hepatic T7αOH and testosterone 15α-hydroxylase activities were enhanced by 70 and 40%, respectively. At the long-term follow-up, benign and malignant lung tumors were observed but in the livers only slightly increased inflammation was found. At the 1.5-year follow-up (cumulated lung dose 0.4-0.66 Gy, 131 and 182 kBq), decreases in lung testosterone 6 beta-hydroxylase (60%) and testosterone 6α-hydroxylase (30%) activities were found, In contrast to lungs, hepatic testosterone 16α-hydroxylase activity decreased by 60-75% with both nonactivated and neutron-activated particles. These findings indicate that when lung is exposed to nonactivated UO2 or β-emitting UO2 particles they have differential effects on CYP enzymes in both the primary target organ (lung) and secondary tissue (liver).