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Abstract
Telomeres could be one of the main targets of several anti-tumour drugs. However, the interaction of these drugs with telomeric DNA sequences has not previously been extensively clarified. Determining the sequence selectivity of DNA damaging agents could elucidate the mechanism of how the drugs work. The implementation of capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) has given rise to sensitive and precise analysis of the sequence specificity of DNA damaging agents.
The first part of this project involved the use of the ABI3730 DNA Analyzer to determine the sequence specificity of cisplatin in purified DNA samples containing telomeric sequences. This technique provided a very accurate analysis of cisplatin-DNA adduct formation in telomeres and non-telomeric DNA sequences.
The second part of this project concerned a comparison of the action of bleomycin in telomeric sequences and non-telomeric sequences (centromeric alpha DNA) in intact human cellular DNA. The experiments with purified HeLa DNA and HeLa cell DNA helped to clarify the mechanism of action of bleomycin in human cellular DNA.