5-Azacytidine (5AzC)-induced histopathological changes in the central nervous system of rat fetuses

Exp Toxicol Pathol. 2002 Aug;54(2):91-6. doi: 10.1078/0940-2993-00239.

Abstract

5-Azacytidine (5AzC) is a cytidine analogue which possesses nitrogen atom instead of carbon atom at the position 5 of the pyrimidine ring. In this study, detailed histopathological changes were sequentially examined in the rat fetal brain obtained from dams treated with 5AzC (10 mg/kg) on day 13 of gestation (GD13). At 6 hours after treatment (HAT), a prominent accumulation of neuroepithelial cells showing pleomorphic mitotic figures were observed in the telencephalic wall. The mitosis-index peaked at 6 HAT, and decreased thereafter. Neuroepithelial cells positive for nick end labeling (TUNEL) method, which is widely used for the detection of apoptotic cells, prominently increased at 9 HAT, and the TUNEL-index peaked at 12 HAT. TUNEL-positive cells showed ultrastructural characteristics of apoptosis. At 24 HAT, the formation of rosette-like structures was observed in the fetal brain. From the results of the present study, it was evident that abnormal mitosis and neuronal apoptosis were induced in the rat fetal brain following 5AzC-administration to dams on GD13. In addition, it is suggested that 5AzC-induced apoptosis might occur mainly in the post mitotic phase of cell cycle.

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / adverse effects*
  • Apoptosis / drug effects*
  • Azacitidine / adverse effects*
  • Brain / drug effects*
  • Brain / embryology
  • Brain / pathology*
  • Embryonic and Fetal Development / drug effects*
  • Female
  • In Situ Nick-End Labeling
  • Mitosis / drug effects
  • Pregnancy
  • Rats
  • Rats, Wistar

Substances

  • Antimetabolites, Antineoplastic
  • Azacitidine