Clastogenic activity of 2-chlorodeoxyadenosine in mammalian somatic cells

• Autor(a) principal: Antonucci,Gilmara Ausech
• Data de Publicação: 2005
• Outros Autores: Takahashi,Catarina Satie
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Genetics and Molecular Biology
• Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S1415-47572005000200027
• topic: human lymphocytes; 2-CdA; chromosomal aberrations; SCE; cell cycle

The base analogue 2-chlorodeoxyadenosine (2-CdA) used for therapy in chronic resistant and advanced lymphoproliferative disorders, is cytotoxic for both dividing and non-dividing lymphocytes. The present work evaluated the clastogenic potential of this drug in vitro in human lymphocytes in culture and in vivo in BALB/c mice bone marrow cells. In human lymphocytes, the clastogenic effect of 2-CdA was studied in G1, S and G2 phases of the cell cycle, using three different concentrations (10, 20 and 40 mug/mL). The endpoints analyzed included mitotic index (MI), proliferation index (PI), sister chromatid exchange (SCE), and chromosomal aberration (CA). Statistical analysis by a variance (ANOVA) test showed a significant increase (p < 0.05) in CA frequencies for cells treated during the S phase, but the MI did not vary. The concentrations tested did not produce a significant increase in the mean frequency of SCEs, nor did they change the cell PI in the G1 and S phases. The concentrations in vivo tested were 0.25, 0.375 and 0.5 mg/kg body weight. In this assay, alterations in CA frequencies and MI were not observed at the dose levels tested. Therefore, the results indicate a clastogenic effect of 2-CdA in human lymphocyte cultures.