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origin of the extra centrosomes was analyzed by addressing the maturity of the
newly formed structures. Typically mature centrosomes, identified by the presence
of Cep170 proteins, are the result of overduplication of pre-existing centrosomes.
Conversely, it is believed that, Cep170 negative, immature centrosomes are the
result of accumulation of the organelles by impaired cytokinesis. Scoring of
Cep170-stained Zidovudine-induced centrosomes revealed that 40, 50, and 53 %
of the supernumerary centrosomes in cells exposed to Zidovudine, respectively,
were mature, compared to 22 % of unexposed cells centrosomes in the control.
Therefore, Zidovudine-induced centrosomal amplification is the result of both
overduplication and cytokinesis impairment (Davila et al.
2009
).
References
Avramis VI, Markson W, Jackson RL, Gomperts E (1989) Biochemical pharmacology of
zidovudine in human T-lymphoblastoid cells (CEM). AIDS 3:417-422
Agarwal RP, Olivero OA (1997) Genotoxicity and mitochondrial damage in human lymphocytic
cells chronically exposed to 3'-azido-2',3'-dideoxythymidine (AZT). Mutat Res 390:223-231
Borojerdi JP, Ming J, Cooch C, Ward Y, Semino-Mora C, Yu M, Braun HM, Taylor BJ, Poirier MC,
Olivero OA (2009) Centrosomal amplification and aneuploidy induced by the antiretroviral drug
AZT in hamster and human cells. Mutat Res 665:67-74
Carroll PE, Okuda M, Horn HF, Biddinger P, Stambrook PJ, Gleich LL, Li YQ, Tarapore P,
Fukasawa K (1999) Centrosome hyperamplification in human cancer: chromosome instability
induced by p53 mutation and/or Mdm2 overexpression. Oncogene 18:1935-1944
Chandrasekaran B, Kute TE, Duch DS (1995) Synchronization of cells in the S phase of the cell
cycle by 3
0
-azido- 3
0
-deoxythymidine: implications for cell cytotoxicity. Cancer Chemother
Pharmacol 35:489-495
St. Clair MH, Richards CA, Spector T, Weinhold KJ, Miller WH, Langlois AJ, Furman PA (1987)
3
0
-Azido-3
0
-deoxythymidine triphosphate as an inhibitor and substrate of purified human
immunodeficiency virus reverse transcriptase. Antimicrob Agents Chemother 31:1972-1977
Copeland WC, Chen MS, Wang TS (1992) Human DNA polymerases alpha and beta are able to
incorporate anti-HIV deoxynucleotides into DNA. J Biol Chem 267:21459-21464
D'Assoro AB, Lingle WL, Salisbury JL (2002) Centrosome amplification and the development of
cancer. Oncogene 21:6146-6153
Davila K, Yu M, Poirier MC, Olivero OA (2009) Centrosomal amplification induced by
nucleoside reverse transcriptase inhibitors (NRTIs) in cultured human breast epithelial MCF
10A cells. Environ Mol Mutagen 50:546
Diwan BA, Riggs CW, Logsdon D, Haines DC, Olivero OA, Rice JM, Yuspa SH, Poirier MC,
Anderson LM (1999) Multiorgan transplacental and neonatal carcinogenicity of 3'-azido-3'-
deoxythymidine in mice. Toxicol Appl Pharmacol 15:82-99
Doxsey S, Zimmerman W, Mikule K (2005) Centrosome control of the cell cycle. Trends Cell
Biol 15:303-311
Dutra A, Pak E, Wincovitch S, John K, Poirier MC, Olivero OA (2010) Nuclear bud formation: a
novel manifestation of Zidovudine genotoxicity. Cytogenet Genome Res 128:105-110
Escobar PA, Olivero OA, Wade NA, Abrams EJ, Nesel CJ, Ness RB, Day RD, Day BW, Meng Q,
O'Neill JP, Walker DM, Poirier MC, Walker VE, Bigbee WL (2007) Genotoxicity assessed by the
comet and GPA assays following in vitro exposure of human lymphoblastoid cells (H9) or
perinatal exposure of mother-child pairs to AZT or AZT-3TC. Environ Mol Mutagen 48:330-343
Fang JL, Beland FA (2000) Development of a novel (32)P-postlabeling method for the analysis of
3'-azido-3'-deoxythymidine. Cancer Lett 153:25-33
