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Induction of DNA fragmentation by total-body irradiation in murine
liver
M. Terashima1, Y. Ogawa1, K. Toda2, N. Hamada1, A. Nishioka1,
T. Inomata1, S. Yoshida1, Y. Shizuta2 and H. Seguchi3
Departments of 1Radiology, 2Medical Chemistry and 32nd
Department of Anatomy and Cell Biology, Kochi Medical School, Kochi, Japan
Offprint requests to: Dr. Yasuhiro
Ogawa, MD., Department of Radiology, Kochi Medical School, Kohasu, Oko-cho,
Nankoku, Kochi 783, Japan
Summary. Total-body irradiation
(TBI) is an accepted modality to treat patients with disseminated tumors.
The influence of the treatment on normal tissues is evaluated using mice
by measuring the rate of the induction and distribution of apoptosis, as
well as DNA fragmentation which occurs in the murine liver within hours
of irradiation.
Unanesthetized female C3H/He mice were exposed to g-ray
TBI of 2, 7, and 20 gray (Gy) delivered from 60Co at a dose rate of 114
cGy/min. Frozen sections of livers which were excised from the animals at
various times after irradiation were stained by hematoxylin-eosin (H-E)
to count numbers of apoptotic cells, or were examined to detect DNA fragmentation.
The percentages of apoptotic cells and length of the period
during which the maximum levels of the percentages were exhibited showed
a dose-dependent increase in the sections stained with H-E. No positive
cells for 3'-OH ends of fragmented DNA were found in the liver before TBI,
whereas positive cells were observed immediately after irradiation without
dose-dependency, these positive cells returned to nearly basal levels after
several hours. Positive cells were observed prior to showing apoptosis,
suggesting that DNA fragmentation occurs immediately after TBI independent
of apoptosis. The difference in the time courses between induction of DNA
fragmentation and of apoptosis was not observed in other organs or in the
samples treated with the detergent. These results suggested that the 3'-OH
ends newly generated by TBI were masked by a detergent-soluble DNA-binding
molecule which might be preferentially present in the murine liver. Histol
Histopathol 13, 379-384 (1998)
Key words: Total-body irradiation,
Murine liver, Apoptosis, DNA fragmentation
DOI: 10.14670/HH-13.379
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