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1977864 
Journal Article 
Apoptosis and S Phase of the Cell Cycle in BeWo Trophoblastic and HeLa Cells are Differentially Modulated by Toxoplasma gondii Strain Types 
Angeloni, MB; Silva, NM; Castro, AS; Gomes, AO; Silva, DAO; Mineo, , JR; Ferro, EAV 
2009 
Placenta
ISSN: 0143-4004
EISSN: 1532-3102 
30 
785-791 
English 
Transplacental transmission of Toxoplasma gondii causes
congenital toxoplasmosis, one of the most severe forms of infection. The ability of the parasite
to survive intracellularly largely depends on the blocking of different proapoptotic signaling
cascades of the host cells. During pregnancy, however, alterations in the incidence of apoptosis
are associated with abnormal placental morphology and function. The aim of this study was to
evaluate the incidence of apoptosis and cell proliferation in trophoblastic (BeWo cell line) and
uterine cervical (HeLa cell line) cells infected with a highly virulent RH strain or a moderately
virulent ME49 strain of T. gondii. BeWo and HeLa cells were infected with RH or ME49 tachyzoites
(2:1 and 5:1; parasite:cell) or medium alone (control). After 2 h, 6 h and 12 h of incubation,
cells were fixed in 10% formalin and analyzed by immunohistochemistry to determine the apoptosis
(expression of cytokeratin 18 neo-epitope - clone M30) and cell in S phase (expression of
proliferating cell nuclear antigen - PCNA) indices. RN strain-infected BeWo and HeLa cells showed
a lower apoptosis index than non-infected controls, whereas a higher apoptosis index was found in
ME49 strain-infected cells compared to controls. In addition, RH-infected cells displayed lower
apoptosis index than ME49-infected cells, even though active caspase-3 was detected in both cell
types infected with either RH or ME49 strains as well in non-infected cells in all analyzed times
of infection. Also, the cell S phase indices were higher in ME49 strain-infected BeWo and HeLa
cells as compared to non-infected controls and RH strain-infected cells. These results indicate
that RH and ME49 strains of T. gondii possess opposing mechanism of interference in apoptosis and
cell cycle S phase of both BeWo and HeLa cells and these differences can be associated to evasion
strategies of the parasite to survive inside the host cells. (C) 2009 Elsevier Ltd. All rights
reserved. 
Toxoplasma gondii; Trophoblast cell; Cell cycle S phase; Apoptosis 
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