Investigating the formation and growth of alpha-particle radiation-induced foci of altered hepatocytes: a model-based approach.
The effect of alpha-particle radiation on the formation and increase in volume of preneoplastic liver lesions was investigated in an animal experiment. Mice were divided into four groups; two groups received different doses of the alpha-particle-labeled antibody (213)Bi-anti CD19 ((213)Bi-CD19), Thorotrast was administered to one group, and one group was left untreated. Hematoxylin and eosin-stained liver sections were evaluated for preneoplastic foci of altered hepatocytes 6, 12 and 17 months after treatment. The density and size distribution of focal transections were described by a mechanistic model for the formation and growth of foci of altered hepatocytes. The negative control and the (213)Bi-CD19 groups were combined to investigate the dose-response relationship for model parameters describing the formation and growth of foci of altered hepatocytes. Although (213)Bi-CD19 was given by single injection, the effect on formation of foci of altered hepatocytes lasted for the entire experiment. Likelihood-ratio tests comparing nested models showed that (213)Bi-CD19 increases the rates of both the formation and growth of foci of altered hepatocytes. Comparing the effects of Thorotrast with those of (213)Bi-CD19 revealed that Thorotrast had an effect similar to that of a low dose of (213)Bi-CD19, but the effect on focus formation was slightly smaller whereas the effect on focus growth was slightly higher for Thorotrast, in contrast to a low dose of (213)Bi-CD19.
Kopp-Schneider
Annette
A
Biostatistics, German Cancer Research Center, 69009 Heidelberg, Germany. kopp@dkfz.de
Haertel
Thomas
T
Burkholder
Iris
I
Bannasch
Peter
P
Wesch
Horst
H
Groos
Jutta
J
Heeger
Steffen
S
D000512:Alpha Particles; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D018941:Antigens, CD19 / Q000737:chemistry / Q000276:immunology; D001729:Bismuth / Q000737:chemistry; D004307:Dose-Response Relationship, Radiation; D022781:Hepatocytes / Q000473:pathology* / Q000528:radiation effects*; D008113:Liver Neoplasms / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D011832:Radiation Injuries / Q000473:pathology; D011868:Radioisotopes
D000906:Antibodies; D018941:Antigens, CD19; D011868:Radioisotopes; D001729:Bismuth