title: Effects of simulated nuclear fuel particles on the histopathology and CYP enzymes in the rat lung and liver.
abstract: 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 7alpha-hydroxylase (T7alphaOH) was decreased by 30% at 3 days treatment with neutron-activated particles (9.3 kBq). At 30 days after treatment, hepatic T7alphaOH and testosterone 15alpha-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 6beta-hydroxylase (60%) and testosterone 6alpha-hydroxylase (30%) activities were found. In contrast to lungs, hepatic testosterone 16alpha-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 beta-emitting UO2 particles they have differential effects on CYP enzymes in both the primary target organ (lung) and secondary tissue (liver).
authors.affiliation: Department of Pharmacology and Toxicology, University of Kuopio, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Pasanen
authors.forename: S
authors.initials: S
authors.lastname: Lang
authors.forename: A
authors.initials: A
authors.lastname: Kojo
authors.forename: V M
authors.initials: VM
authors.lastname: Kosma
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D005500:Follow-Up Studies; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology / Q000528:radiation effects; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D009381:Neoplasms, Radiation-Induced; D009502:Neutrons; D010316:Particle Size; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism; D014132:Trachea / Q000187:drug effects / Q000378:metabolism; D017974:Uranium Compounds / Q000633:toxicity*
chemical_list: D017974:Uranium Compounds; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; C022724:testosterone 7-alpha-hydroxylase, hamster; C012597:uranium dioxide