Apoptosis and DNA fragmentation as induced by tertiary butylhydroperoxide in the brain

Brain Research Bulletin
S K MukherjeeJ D Adams

Abstract

In this study, the effect of intracerebroventricular administration of the free radical generator, tertiary butylhydroperoxide, on DNA, was quantitated. Previous studies had established DNA as a very important site of free radical attack. The purpose of the study was to detect whether DNA was one of the primary targets of the toxin as well as to detect any apoptosis that may have been induced by the toxin. The DNA fragmentation assay clearly showed DNA damage within 20 min of administration of 109.7 mg/kg t-BuOOH almost in all brain regions in both 2-month and 8-month-old C57BL/6 mice. In Situ Apoptosis Detection assay, where brain sections were stained with Apoptag, demonstrated that t-BuOOH induces apoptosis in many brain regions. Electron microscopy was done to show nuclear damage and DNA fragments appearing in the cytoplasm. Cresyl violet staining was done to show that while low dose (21.9 mg/kg) t-BuOOH induces apoptosis, it may also induce necrosis in other cells of the same brain region. Thus, from this study we can conclude that DNA may be one of the primary target sites of free radical attack in the brain, and results in both necrosis and apoptosis. This can have a profound effect on neurodegeneration.

References

Jan 1, 1975·Annual Review of Biochemistry·I Fridovich
Sep 15, 1975·European Journal of Biochemistry·H Sies, K H Summer
Nov 1, 1991·Experimental Cell Research·D M OjciusJ D Young
May 1, 1989·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·D J McConkeyS Orrenius
Aug 1, 1988·International Journal of Radiation Biology·G W TeeborJ Cadet
Jun 3, 1988·Science·J A Imlay, S Linn
May 1, 1985·Toxicology and Applied Pharmacology·G F RushW R Hewitt
Feb 4, 1974·Biochemical and Biophysical Research Communications·R IshidaT Takahashi
Jun 1, 1994·Molecular and Chemical Neuropathology·J D AdamsA Kuda
Jun 1, 1994·Free Radical Biology & Medicine·V J ForrestN Ramakrishnan
Dec 1, 1993·Stroke; a Journal of Cerebral Circulation·M D LinnikM D Hatfield
Aug 1, 1993·Free Radical Biology & Medicine·J D AdamsD Shah

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Citations

May 1, 1997·Molecular and Chemical Neuropathology·M L Chang, J D Adams
Mar 31, 2004·Toxicology and Applied Pharmacology·Pramod K AllaniManisha Sonee
Jul 2, 1997·European Journal of Pharmacology·S K MukherjeeJ D Adams
Jun 5, 2003·Neurotoxicology·Manisha SoneeSuman K Mukherjee
May 9, 2001·Biochimica Et Biophysica Acta·L K KlaidmanJ D Adams
Aug 15, 2002·Experimental Gerontology·Yingpei ZhangBrian Herman
Jan 1, 2013·Journal of Otology·Ding DalianMasaru Tanokura
Nov 5, 1999·Free Radical Research·Y Hiraku, S Kawanishi
Jan 1, 2006·Toxicology Mechanisms and Methods·Suraj G BhansaliSuman K Mukherjee

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