In:
The Journal of Neuroscience, Society for Neuroscience, Vol. 16, No. 21 ( 1996-11-01), p. 6795-6806
Abstract:
To determine whether oxidative stress after cerebral ischemia–reperfusion affects genetic stability in the brain, we studied mutagenesis after forebrain ischemia–reperfusion in Big Blue transgenic mice (male C57BL/6 strain) containing a reporter lac I gene, which allows detection of mutation frequency. The frequency of mutation in this reporter lac I gene increased from 1.5 to 7.7 (per 100,000) in cortical DNA after 30 min of forebrain ischemia and 8 hr of reperfusion and remained elevated at 24 hr reperfusion. Eight DNA lesions that are characteristic of DNA damage mediated by free radicals were detected. Four mutagenic lesions (2,6-diamino-4-hydroxy-5-formamidopyrimidine, 8-hydroxyadenine, 5-hydroxycytosine, and 8-hydroxyguanine) examined by gas chromatography/mass spectrometry and one corresponding 8-hydroxy-2′-deoxyguanosine by a method of HPLC with electrochemical detection increased in cortical DNA two- to fourfold ( p 〈 0.05) during 10–20 min of reperfusion. The damage to γ-actin and DNA polymerase-β genes was detected within 20 min of reperfusion based on the presence of formamidopyrimidine DNA N -glycosylase-sensitive sites. These genes became resistant to the glycosylase within 4–6 hr of reperfusion, suggesting a reduction in DNA damage and presence of DNA repair in nuclear genes. These results suggest that nuclear genes could be targets of free radicals.
Type of Medium:
Online Resource
ISSN:
0270-6474
,
1529-2401
DOI:
10.1523/JNEUROSCI.16-21-06795.1996
Language:
English
Publisher:
Society for Neuroscience
Publication Date:
1996
detail.hit.zdb_id:
1475274-8
SSG:
12
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