Effect of streptozotocin on interstitial telomeric sequences of Chinese hamster ovary cells

QUIROGA, I.Y.; PAVIOLO, N.S.; BOLZÁN, A.D.

Buenos Aires

Workshop; Third South American Workshop on new trends in advanced fluorescence microscopy techniques; 2011

Universidad de Buenos Aires

The relationship between interstitial telomeric sequences and the chromosomal aberrations induced by the methylating compound streptozotocin (STZ) was investigated in Chinese hamster ovary (CHO) cells. Fluorescence in situ hybridization (FISH) with a PNA telomeric probe (TTAGGG)n was applied on chromosome preparations of CHO cells treated with 0-4mM STZ during 30 minutes at 37°C. Chromosomal aberrations were analyzed in cells harvested 18 h (first mitosis) after treatment. Our results show that STZ induces both chromosome- and chromatid-type aberrations, in a concentration-dependent manner (p<0.05), and that 41 % of the total aberrations induced by STZ in CHO cells exhibited one or more FISH-detectable telomeric signals. This finding suggests that interstitial telomeric sequences are preferentially involved in the chromosome damage induced by STZ, taking into account that these sequences cover only about 3% of the CHO karyotype. Moreover, our results show that 4mM STZ induces chromosome breaks at centromeric regions of CHO chromosomes, and that 19% of these breaks involve dissociation of the telomeric signal, indicating that STZ is capable of inducing breakage within centromeric blocks of interstitial telomeric sequences. Additional data will be needed to determine if, like other chemical mutagens, STZ induces translocation and/or amplification of telomeric sequences.