Abstract for presentation at 11th International Congress of Human Genetics

Effects of the anticancer drug cisplatin on human BRCA1 gene: cellular DNA repair and transcriptional transactivation activity

  • A/Prof Dr Adisorn Ratanaphan, Laboratory of Pharmaceutical Biotechnology, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince, Thailand
  • Mr Siriwat Wasiksiri, Laboratory of Pharmaceutical Biotechnology, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince, Thailand
  • Dr Bhutorn Canyuk, Laboratory of Pharmaceutical Biotechnology, Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince, Thailand

    • We investigated the functional consequences of cisplatin-treated BRCA1 gene. The cellular proficiency in repairing the drug-treated DNA was evaluated specifically in the 3,426-bp fragment of the BRCA1 exon 11 of the MCF-7 cells using the semi-quantitative PCR assay. Over 80% of the lesions were removed by 18 h after cellular treatment with 50 uM cisplatin for 6 h. However, repair of only 30% of the lesions was observed at higher cisplatin concentration of 200 uM. The transcriptional transactivation activity of the BRCT protein, when tested in the GAL4 transcriptional activation system, was inversely proportional to the amount of platinum-BRCA1 adducts. A significant decrease in the transcriptional transactivation activity of the drug-treated BRCA1 was observed with the adduction of approximate 1-2 platinum atoms, potentially at the preferential d(GpG) sequence of unique Eco0109I-cleaved site of the BRCA1 gene.

    Conference Organiser - ICMS Pty Ltd