Toxicology of intrahepatic arterial administration of interventional phosphorus-32 glass microspheres to domestic pigs.
OBJECTIVE
To evaluate the toxic response to intrahepatic arterial administration of radioactive phosphorus-32 glass microspheres (32P-GMS) in domestic pigs.


METHODS
Through selective catheterization of hepatic artery, 32P-GMS was infused to 5 healthy domestic pigs in a dosage equivalent to the therapeutic dose for human being, and 31P-GMS was infused to other 5 healthy domestic pigs. Two pigs served as the whole course blank controls. One pig from each group was surrendered to euthanasia at week 1, 2, 4, 8 and 16, respectively, and liver biopsies were performed on the rest of pigs at the corresponding time points. Liver tissues from different sites were taken for light and electron microscopy. The ultrastructural histopathological changes were evaluated semiquantitatively.


RESULTS
The accumulative amount of 32P-GMS in the target tissue attained more than 90% of the total dose administrated. Histologically, abnormal hepatocytes were easily found at week 1 or 2. At week 4 they were less than at week 1 or 2, and endothelium of the sinuses were damaged prominently. At week 8 they were scarcely seen, and liver tissue recovered gradually. The histological features of liver tissue restored to normal at week 16. Semiquantitative analysis of ultrastructural morphology in the experimental group showed no statistical difference (P > 0.50) between the nuclear abnormality (Nabn) and mitochrondrial variability (Mvar) at week 1 or 2, but revealed prominent difference (P < 0.01, P < 0.001) as compared with those in other groups. In the experimental group the Nabn in tissues showed no significant difference (P > 0.20) between week 8 and week 16.


CONCLUSIONS
32P-GMS internal irradiation at the dosage equivalent to human therapeutic dosage exerts reversible injury to domestic pig liver tissue, and it takes more than 8 weeks for the injured liver tissue to recover.
Liu
L
L
Institute of Medical Science, Nanjing Railway Medical College, Nanjing 210009, China.
Teng
G
G
Zhang
D
D
Song
J
J
He
S
S
Guo
J
J
Fang
W
W
D000818:Animals; D005260:Female; D005898:Glass; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000648:ultrastructure*; D008297:Male; D008863:Microspheres; D010761:Phosphorus Radioisotopes / Q000008:administration & dosage / Q000633:toxicity*; D011829:Radiation Dosage; D011897:Random Allocation; D013552:Swine
D010761:Phosphorus Radioisotopes