Effect of eflornithine on mutation frequency in temozolomide-treated U87MG cells

Oncotarget
Noymi YamVictor A Levin

Abstract

Treatment of infiltrative glioma presents a number of unique challenges due to poor penetration of typical chemotherapeutic agents into the infiltrating edge of tumors. The current chemotherapy options include nitrosoureas (e.g., lomustine) and the imidazotetrazine-class monofunctional DNA alkylating agent, temozolomide (TMZ). Both classes of drugs alkylate DNA and have relatively unrestricted passage from blood into brain where infiltrative tumor cells reside. Recent research indicates that secondary mutations detected in the RB and AKT-mTOR signaling pathways are linked to characteristics of recurrent tumors specific to TMZ-treated patients. It has been hypothesized that a decrease in rate of secondary mutations may result in delay of tumor recurrence. To that end, this study was designed to test viability of decreasing secondary mutations by disrupting the cell division cycle using eflornithine, a specific inhibitor of ornithine decarboxylase. U87MG glioblastoma cell line characterized by chromosomal abnormalities commonly attributed to primary cancers was used as a model for this study. The cells were subjected to TMZ treatment for 3 days followed by eflornithine (DFMO) treatment for 4 or 11 days. It was shown that TMZ sign...Continue Reading

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Methods Mentioned

BETA
Exon-Seq
Assay
PCR

Software Mentioned

DFMO

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