THE TURNOVER OF ISOTOPICALLY LABELLED DNA IN VIVO IN DEVELOPING, ADULT AND SCRAPIE‐AFFECTED MOUSE BRAIN

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Abstract
Abstract— Tracer experiments using [3H]thymidine have shown that a large proportion of the DNA synthesized in control and scrapie‐affected mouse brain is metabolically unstable. Although the turnover of mitochondrial DNA contributed to the loss of radioactivity from whole brain, it has been shown that 70 per cent of the labelled nuclear DNA was removed between 1 and 21 days after injecting the isotopic precursor. Observations on developing mouse brain, where the rate of DNA synthesis is far higher than that in adult brain, also revealed the existence of metabolically unstable DNA. Similar studies on developing and adult brain using [14C]thymidine indicated that most of the radioactivity lost in vivo was not due to radiation damage to newly labelled DNA molecules. Hydroxyapatite chromatography of heat denatured and renatured DNA from adult brain showed that the rates of turnover of the poorly, moderately and highly reiterated species of nuclear DNA were similar. The results of some dissection experiments have further shown that the observed breakdown of DNA in adult brain was not specifically associated with the turnover of subependymal cells. It is suggested that a metabolically labile fraction of nuclear DNA is present in developing and adult mouse brain and that the amount of tracer incorporated into this fraction is increased in mice infected with scrapie.