title: Investigating the formation and growth of alpha-particle radiation-induced foci of altered hepatocytes: a model-based approach.
abstract: 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.
authors.affiliation: Biostatistics, German Cancer Research Center, 69009 Heidelberg, Germany. kopp@dkfz.de
authors.forename: Annette
authors.initials: A
authors.lastname: Kopp-Schneider
authors.forename: Thomas
authors.initials: T
authors.lastname: Haertel
authors.forename: Iris
authors.initials: I
authors.lastname: Burkholder
authors.forename: Peter
authors.initials: P
authors.lastname: Bannasch
authors.forename: Horst
authors.initials: H
authors.lastname: Wesch
authors.forename: Jutta
authors.initials: J
authors.lastname: Groos
authors.forename: Steffen
authors.initials: S
authors.lastname: Heeger
mesh_terms: 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
chemical_list: D000906:Antibodies; D018941:Antigens, CD19; D011868:Radioisotopes; D001729:Bismuth