2005Journal of Clinical OncologyRequires access

Expression of ERCC1 and XPA has demonstrated that cisplatin is more toxic than oxaliplatin in oesophageal adenocarcinoma cells

Rao Khalid Mehmood, K. M. Sales, Sas Dijk, Marc C. Winslet

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Abstract

4251 Background: Xeroderma Pigmentosum protein A (XPA), recognises DNA damage, its low levels with decreased expression of Excision Repair Cross Complementing 1(ERCC1), an endonuclease of Nucletide excision repair pathway, were found responsible for pronounced cisplatin sensitivity. While increased levels of XPA and ERCC1has demonstrated cisplatin resistance. We want to compare the levels of XPA and ERCC1 gene expression in oesophageal adenocarcinoma cells (OE33) after treating them with cisplatin and oxaliplatin. Methods: Lethal doses 50 (LD50) of oxaliplatin and cisplatin in OE 33 cells for 24 hours were determined by the alamarBlue assay. Cells were treated with that LD50 at 2, 4, 6 and 24 hours. Using RT-PCR and specific primers, expression of ERCC1 and XPA gene levels with cisplatin and oxaliplatin treatments were compared at 2, 4, 6 and 24 hours interval, by Syngene Gene Tools programme. Results: XPA was undetectable with cisplatin treatment, while it was overtly expressed with oxaliplatin treatment at all time intervals. Small amounts of ERCC1 were seen in 2, 6 and 24 hours with below detectable levels at 4 hours after cisplatin treatment. In contrast, it was over expressed with oxaliplatin treatment at all time intervals Conclusions: XPA and ERCC1 were over expressed with oxaliplatin treatment while in cisplatin treatment they were nearly undetectable. These findings suggest that cisplatin is more toxic in oesophageal adenocarcinoma cells than oxaliplatin. No significant financial relationships to disclose.

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4251 Background: Xeroderma Pigmentosum protein A (XPA), recognises DNA damage, its low levels with decreased expression of Excision Repair Cross Complementing 1(ERCC1), an endonuclease of Nucletide excision repair pathway, were found responsible for pronounced cisplatin sensitivity. While increased levels of XPA and ERCC1has demonstrated cisplatin resistance. We want to compare the levels of XPA and ERCC1 gene expression in oesophageal adenocarcinoma cells (OE33) after treating them with cisplatin and oxaliplatin. Methods: Lethal doses 50 (LD50) of oxaliplatin and cisplatin in OE 33 cells for 24 hours were determined by the alamarBlue assay. Cells were treated with that LD50 at 2, 4, 6 and 24 hours. Using RT-PCR and specific primers, expression of ERCC1 and XPA gene levels with cisplatin and oxaliplatin treatments were compared at 2, 4, 6 and 24 hours interval, by Syngene Gene Tools programme. Results: XPA was undetectable with cisplatin treatment, while it was overtly expressed with oxaliplatin treatment at all time intervals. Small amounts of ERCC1 were seen in 2, 6 and 24 hours with below detectable levels at 4 hours after cisplatin treatment. In contrast, it was over expressed with oxaliplatin treatment at all time intervals Conclusions: XPA and ERCC1 were over expressed with oxaliplatin treatment while in cisplatin treatment they were nearly undetectable. These findings suggest that cisplatin is more toxic in oesophageal adenocarcinoma cells than oxaliplatin. No significant financial relationships to disclose.

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Available abstract

4251 Background: Xeroderma Pigmentosum protein A (XPA), recognises DNA damage, its low levels with decreased expression of Excision Repair Cross Complementing 1(ERCC1), an endonuclease of Nucletide excision repair pathway, were found responsible for pronounced cisplatin sensitivity. While increased levels of XPA and ERCC1has demonstrated cisplatin resistance. We want to compare the levels of XPA and ERCC1 gene expression in oesophageal adenocarcinoma cells (OE33) after treating them with cisplatin and oxaliplatin. Methods: Lethal doses 50 (LD50) of oxaliplatin and cisplatin in OE 33 cells for 24 hours were determined by the alamarBlue assay. Cells were treated with that LD50 at 2, 4, 6 and 24 hours. Using RT-PCR and specific primers, expression of ERCC1 and XPA gene levels with cisplatin and oxaliplatin treatments were compared at 2, 4, 6 and 24 hours interval, by Syngene Gene Tools programme. Results: XPA was undetectable with cisplatin treatment, while it was overtly expressed with oxaliplatin treatment at all time intervals. Small amounts of ERCC1 were seen in 2, 6 and 24 hours with below detectable levels at 4 hours after cisplatin treatment. In contrast, it was over expressed with oxaliplatin treatment at all time intervals Conclusions: XPA and ERCC1 were over expressed with oxaliplatin treatment while in cisplatin treatment they were nearly undetectable. These findings suggest that cisplatin is more toxic in oesophageal adenocarcinoma cells than oxaliplatin. No significant financial relationships to disclose.

Key concepts: ERCC1, Cisplatin, Oxaliplatin, Xeroderma pigmentosum, Nucleotide excision repair, Cancer research, DNA repair, Medicine

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