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Apoptotic cell death and cell proliferative
activity in the rat fetal central nervous system from dams administered
with ethylnitrosourea (ENU)
K. Katayama, K. Uetsuka, N. Ishigami, H. Nakayama and K. Doi
Department of Veterinary Pathology, Graduate School of Agricultural
and Life Sciences, The University of Tokyo, Yayoi, Bunkyo-ku,
Tokyo, Japan
Offprint requests to: Dr.
Kei-ichi Katayama, Department of Veterinary Pathology, Graduate
School of Agricultural and Life Sciences, The University of Tokyo,
1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8567 Japan
Summary. Ethylnitrosourea (ENU), a well known DNA alkylating
agent, induces anomalies in the central nervous system (CNS),
craniofacial tissues and male reproductive organs, and the enhancement
of apoptosis is found in these tissues immediately after the administration
of ENU (Katayama et al., 2000a). In this study, pregnant rats
were treated with 60mg/kg of ENU at day 13 of gestation, and kinetics
of apoptotic cells, mitotic cells and bromodeoxyuridine (BrdU)-positive
cells in the fetal CNS were examined from 3 to 48 hours after
the treatment (HAT). From 3 HAT, a significant increase in the
number of apoptotic cells and a significant decrease in the number
of mitotic cells were detected in the fetal CNS, and BrdU-positive
cells significantly decreased in accordance with the increase
in the number of apoptotic cells. The present results strongly
suggest that both excess cell death by apoptosis and cell growth
arrest indicated by decreased number of mitotic cells and BrdU-positive
cells may have a close relation to the later occurrence of microencephaly
following ENU-administration, and that ENU affects mainly S-phase
cells and causes apoptosis. Histol. Histopathol. 16, 79-85
(2001)
Key words: Apoptosis, Cell growth arrest, Ethylnitrosourea,
Fetus, Rat
DOI: 10.14670/HH-16.79
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