EFFECTS OF SIMULATED NUCLEAR-FUEL PARTICLES ON THE HISTOPATHOLOGY ANDCYP 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) o n the rat lung and liver histopathology and cytochrome P450 (CYP) acti vities. In the short-term study, after a single intratracheal instilla tion with neutron-activated particles (administered activity 36 kBq), the lung histology revealed inflammation and a decrease in several lun g testosterone hydroxylation levels. Liver exhibited normal histology but hepatic testosterone 7 alpha-hydroxylase (T7 alpha OH) was decreas ed by 30% at 3 days treatment with neutron-activated particles (9.3 kB q). At 30 days after treatment, hepatic T7 alpha OH and testosterone 1 5 alpha-hydroxylase activities were enhanced by 70 and 40%, respective ly, At the long-term follow-up, benign and malignant lung tumors were observed but in the livers only slightly increased inflammation was fo und. At the 1.5-year follow-up (cumulated lung dose 0.4-0.66 Gy, 131 a nd 182 kBq), decreases in lung testosterone 6 beta-hydroxylase (60%) a nd testosterone 6 alpha-hydroxylase (30%) activities were found, In co ntrast to lungs, hepatic testosterone 16 alpha-hydroxylase activity de creased by 60-75% with both nonactivated and neutron-activated particl es. These findings indicate that when lung is exposed to nonactivated UO2 or beta-emitting UO2 particles they have differential effects on C YP enzymes in both the primary target organ (lung) and secondary tissu e (liver). (C) 1995 Academic Press, Inc.