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Abstract

Pathological processes like cancer, chronic inflammation and autoimmune phenomena, all of which involve massive cell death, are associated with significant increases in circulating DNA. In order to clarify whether massive apoptosis occurring under physiological circumstances also causes DNA release into the circulation, we correlated the time-course of dexamethasone-induced intra thymic cell apoptosis with plasma DNA dynamics in rats. Animals were given 10 mg/l dexamethasone in their drinking water for up to 7 days. Sequential plasma samples were obtained during the treatment and DNA was quantitated by a micro fluorometric assay. Thymus and spleen weight as well as apoptotic cell levels were assessed at different times. Seven days of glucocorticoid treatment reduced thymic and spleen mass by 82 and 31%, respectively. Intra thymic apoptosis was maximal 24 h after the beginning of glucocorticoid treatment, declining markedly by 48 h. Very little apoptosis was observed in the spleen. Plasma DNA increased steadily during the first 4 days of glucocorticoid treatment (11.8 +/- 1.2 microg/ml on day 0; 24.2 +/- 1.6 microg/ml on day 4) beginning to decline afterward. Thymectomy but not splenectomy, drastically reduced the glucocorticoid-induced increase in plasma DNA. It is concluded that hormone-induced massive intra thymic cell death is followed by a delayed release of nucleosomal DNA into the circulation.

Aberrant reduction of telomere repetitive sequences in plasma cell-free DNA for early breast cancer detection

“…In addition, it is speculated that telomeric cfDNA levels might be influenced by interweaving factors such as metabolic regulation, hormone balance, and nuclease activity levels in the bloodstream [ 54 – 56 ]. In fact, our results show that telomeric cfDNA levels in the healthy control group were quite variable (range: 34.42 – 274.51, mean: 115.57, as T/R copy ratio), even though we carefully selected the control group by eliminating any potential confounding factors (see Materials and Methods).…”

Hypophysotropic activity of histone H3 in vitro

“…Also supportive of the idea that histones may act as extracellular messengers is the fact that, in the receptive stage of the luteal phase, the human endometrium releases, along with several other proteins, histones H2A, H2B, H3, and H4 [4]. Two days after dexamethasone administration in the drinking water of rats, a significant increase occurs in plasma levels of nucleosomal DNA, which peaks on day 4 [21]. This DNA is mainly of thymic origin where dexamethasone induces massive thymocyte death.…”

The possible protective role of barley seeds on the spleen after administration of glucocorticoids in adult albino rats: A histological and immunohistochemical study

“…Others reported that GCs reduce spleen weight up to 31%. [23] Another study done in asthma mouse models used GC (either systemic or localized) treatment-induced thymic atrophy, also they demonstrate that GCs decrease T regulatory cells numbers and activity indifferent asthma mouse models, probably by reducing thymic production of T Cells. [24]…”