Chromosomal aberrations induced by 5-azacytidine combined with VP-16 (etoposide) in CHO-K1 and XRS-5 cell lines.
A cytogenetic study was carried out with 5-azacytidine (5-azaC) and etoposide (VP-16) in CHO-K1 and XRS-5 (mutant cells deficient for double-strand break rejoining) cell lines to verify the interaction effects of the drugs in terms of induction of chromosomal aberrations. 5-azaC is incorporated into DNA causing DNA hypomethylation, and VP-16 (inhibitor of topoisomerase II enzyme) is a potent clastogenic agent. Cells in exponential growth were treated with 5-azaC for 1 h, following incubation for 7 h, and posttreatment with VP16 for the last 3 h. In K1 cells, the combined treatments induced a significant reduction in the aberrations induced in the X and "A" (autosome) chromosomes, which are the main target for 5-azaC. However, in XRS-5 cells, the drug combination caused a significant increase in the aberrations induced in those chromosomes, but with a concomitant reduction in the randomly induced-aberrations. In addition, each cell line presented characteristic cell cycle kinetics; while the combined treatment induced an S-arrest in K1 cells, alterations in cell cycle progression were not found for XRS-5, although each drug alone caused a G2-arrest. The different cell responses presented by the cell lines may be explained on the basis of the evidence that alterations in chromatin structure caused by 5-aza-C probably occur to a different extent in K1 and XRS-5 cells, since the mutant cells present a typical hyper-condensed chromosome structure (especially the X- and "A" chromosomes), but, alternatively, 5-aza-C could induce reactivation of DNA repair genes in XRS-5 cells.
Guimarães
A P A
AP
Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, SP, Brasil.
Dias
F L
FL
Cardoso
R S
RS
Kronka
S N
SN
Sakamoto-Hojo
E T
ET
D000818:Animals; D001374:Azacitidine / Q000633:toxicity*; D016466:CHO Cells / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002869:Chromosome Aberrations / Q000139:chemically induced*; D006224:Cricetinae; D020732:Cytogenetic Analysis / Q000379:methods; D004338:Drug Combinations; D004347:Drug Interactions / Q000235:genetics; D005047:Etoposide / Q000633:toxicity*; D007700:Kinetics; D009153:Mutagens / Q000633:toxicity; D011836:Radiation Tolerance / Q000235:genetics
D004338:Drug Combinations; D009153:Mutagens; D005047:Etoposide; D001374:Azacitidine