Relative biological effectiveness of carbon ions for causing fatal liver failure after partial hepatectomy in mice.
To evaluate the acute phase damage to liver by carbon ions, BALB/c mice were irradiated with carbon ions or X-rays after two-thirds partial hepatectomy, and their survival was followed. The 50% lethal dose within 60 days (LD50/60) was 42.2 +/- 0.25 Gy (standard error) for X-rays, and 22.7 +/- 0.25 Gy for carbon ions. The relative biological effectiveness (RBE) of carbon ions was 1.86 (95% confident limits: 1.69-2.04) as calculated from the LD50/60. Mice irradiated at much higher doses, 60 Gy of X-rays or 24 Gy of carbon ions, showed significantly higher serum ammonia levels and lower serum albumin levels than normal, suggesting hepatic failure as a cause of death. Hepatocytes showed karyorrhexis and karyolysis in carbon ion irradiated and spotty necrosis in X-ray irradiated mice, suggesting nuclear damage. Mice irradiated with LD50 of X-rays or carbon ions had a remarkably lower bromodeoxyuridine (BrdU) labeling index and mitotic index than control. Treatments with both BrdU and vincristine showed that none of the hepatocytes that synthesized DNA after irradiation completed mitosis, indicating G2 arrest. The liver weight of irradiated mice significantly decreased depending on the dose. Carbon ions as well as X-rays damaged hepatocytes directly and suppressed liver regeneration leading to fatal liver failure.
Tomizawa
M
M
Division of Radiation Medicine, National Institute of Radiological Sciences, Chiba, Japan. nihminor-cib@umin.ac.jp
Miyamoto
T
T
Kato
H
H
Otsu
H
H
D000641:Ammonia / Q000097:blood; D000818:Animals; D001973:Bromodeoxyuridine / Q000032:analysis; D002244:Carbon / Q000009:adverse effects*; D004249:DNA Damage; D004261:DNA Replication / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D020450:Heavy Ions / Q000009:adverse effects*; D006498:Hepatectomy; D022781:Hepatocytes / Q000528:radiation effects; D007928:Lethal Dose 50; D008099:Liver / Q000473:pathology / Q000528:radiation effects*; D017093:Liver Failure / Q000097:blood / Q000209:etiology* / Q000473:pathology; D008115:Liver Regeneration / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000097:blood / Q000209:etiology* / Q000473:pathology; D012062:Relative Biological Effectiveness; D012709:Serum Albumin / Q000172:deficiency; D014750:Vincristine / Q000494:pharmacology; D014965:X-Rays
D012709:Serum Albumin; D014750:Vincristine; D002244:Carbon; D000641:Ammonia; D001973:Bromodeoxyuridine