Loss of Mitochondrial DNA by Gemcitabine Triggers Mitophagy and Cell Death.

Gemcitabine (2,2-difluorodeoxycytidine nucleic acid), an anticancer drug exhibiting a potent ability to kill cancer cells, is a frontline chemotherapy drug. Although some chemotherapeutic medicines are known to induce nuclear DNA damage, no investigation into mitochondrial DNA (mtDNA) damage currently exists. When we treated insulinoma pancreatic ß-cells (line INS-1) with high mitochondrial activity with gemcitabine for 24 h, the mtDNA contents were decreased. Gemcitabine induced a decrease in the number of mitochondria and the average potential of mitochondrial membrane in the cell but increased the superoxide anion radical levels. We observed that treatment with gemcitabine to induce cell death accompanied by autophagy-related protein markers, Atg5 and Atg7; these were significantly prevented by the autophagy inhibitors. The localization of Atg5 co-occurred with the location of mitochondria with membranes having high potential and mitophagy in cells treated with gemcitabine. The occurrence of mitophagy was inhibited by the inhibitors of the phosphatidylinositol 3-kinase/Akt pathway. Our results led us to the conclusion that gemcitabine induced cell death through mitophagy with the loss of mtDNA. These findings may provide a rationale for the combination of mtDNA damage with mitophagy in future clinical applications for cancer cells.

Emission of volatile organic compounds from solid waste disposal sites and importance of heat management.

The emission of volatile organic compounds (VOCs) from a solid waste disposal site for municipal solid wastes was quantified. The VOCs contained in the landfill gas taken at the site were benzene, toluene, xylenes, ethyl benzenes, and trimethyl benzenes, while the concentrations of chlorinated compounds were very low. The concentration of benzene in the landfill gas samples ranged from below the detection limit to 20 mg m(-3), and the ratio of benzene to toluene ranged from 0.2 to 8. The higher concentrations of VOCs in landfill gas and in leachates were observed with the samples taken at high temperature areas of the target site. Polystyrene plastic waste was identified as one of the sources of VOCs in solid waste disposal sites at a high temperature condition. The appropriate heat management in landfill sites is an important countermeasure to avoid unusually high emission of VOCs because the heat generated by the biodegradation of organic solid wastes may promote the release of VOCs, especially in the case of sites which receive both biodegradable and plastic wastes.