Mitochondrial DNA Depletion Induces Radioresistance by Suppressing G2 Checkpoint Activation in Human Pancreatic Cancer Cells

Overview

Journal Radiat Res

Specialties Genetics
Radiology

Date 2009 Jul 8

PMID 19580493

Citations 23

Authors

Carla R Cloos

David H Daniels

Amanda Kalen

Katee Matthews

Juan Du

Prabhat C Goswami

Joseph J Cullen

Affiliations

Soon will be listed here.

Abstract

We hypothesized that mitochondrial function regulates cell cycle checkpoint activation and radiosensitivity. Human pancreatic tumor cells (MiaPaCa-2, rho(+)) were depleted of mitochondrial DNA (rho degrees ) by culturing cells in the presence of ethidium bromide. Depletion of mitochondrial DNA was verified by PCR amplification of total DNA using primer pairs specific for mitochondrial DNA. Loss of mitochondrial DNA decreased plating efficiency and the percentage of cells in S phase. Exponential cultures were irradiated with 2, 4 and 6 Gy (dose rate: 0.83 Gy/min) of ionizing radiation and harvested for determination of cell viability, growth and cell cycle phase distributions. Rho degrees cells were radioresistant compared to rho(+) cells, with a dose-modifying factor (DMF) of 1.6. Although cell growth was significantly inhibited in irradiated rho(+) cells compared to unirradiated control cells, the inhibition in Rho degrees cells was minimal. In addition, mitochondrial DNA depletion suppressed radiation-induced G(2) checkpoint activation, which was accompanied by increases in both cyclin B1 and CDK1. These results suggest that mitochondrial function may regulate cell cycle checkpoint activation and radiosensitivity in pancreatic cancer cells.

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