Journal of Toxicologic Pathology
Online ISSN : 1881-915X
Print ISSN : 0914-9198
ISSN-L : 0914-9198
Originals
1-β-D-Arabinofuranosylcytosine (Ara-C)-induced Apoptosis in the Rat Fetal Tissues and Placenta
Hirofumi YamauchiKei-ichi KatayamaAkira YasoshimaKoji UetsukaHiroyuki NakayamaKunio Doi
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Keywords: Ara-C, apoptosis, fetus, placenta, rat
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2003 Volume 16 Issue 4 Pages 223-229

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Abstract

1-β-D-Arabinofuranosylcytosine (Ara-C), a cytidine analogue, inhibits DNA synthesis and is used for the treatment of myelogenous leukemia. On the other hand, it is also known that Ara-C has a teratogenic effect. In the present study, pregnant rats were treated with 250 mg/kg of Ara-C on day 13 of gestation, and fetal tissues and placentae were collected from 3 to 48 hours after treatment to examine the sequential histopathological changes induced by prenatal Ara-C treatment. The weights of fetuses and placentae and the thickness of the placental labyrinth zone were significantly reduced at 48 hours after treatment. In the fetal tissues such as central nervous system and mesenchymes and in the placental labyrinth zone, the number of pyknotic cells stained positively by the TUNEL method increased markedly after treatment with Ara-C. In most fetal tissues, the number began to increase from 3 to 6 hours and peaked at 9 to 12 hours after treatment. In the placental labyrinth zone, the number peaked at 6 hours after treatment. Electron microscopical features of the pyknotic cells consisted with the ultrastructural characteristics of apoptotic cells. In various fetal organs and placentae, abnormal induction of apoptosis is suggested to induce growth inhibition and have a certain relation to the malformations. Moreover, abnormal induction of apoptosis would have a deep connection with the cytotoxic effect of Ara-C which may affect proliferative cells in fetuses and placentae developing rapidly.

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© 2003 The Japanese Society of Toxicologic Pathology
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