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Extensive DNA damage leads to the activation of poly(ADP-ribose) polymerase and subsequently to the formation of poly(ADP-ribose). When the damage is severe or leads to cell death, poly(ADP-ribose) may leak into the blood circulation. The metabolism of poly(ADP-ribose) in the bloodstream is not well understood. Thus, in the present study, the metabolism of P-labeled poly(ADP-ribose) was followed in mice after injection of this labeled compound into the tail vein. The results showed that 5 min after injection more than half of the radioactivity was concentrated in acid-soluble fractions, namely in low molecular weight compounds in the blood, liver, and kidneys. Most of this radioactivity was in the form of inorganic phosphate, detected 5 min post-injection in the blood, kidneys, and urine. By contrast, the metabolites ADP-ribose and phosphoribosyl-AMP were not detected in any of the tissues nor in blood or urine. Taken together, these findings suggest that once poly(ADP-ribose) enters the bloodstream it is rapidly degraded, thereby preventing its accumulation in the blood.

Citation

Yasuhisa Okajima, Tomoko Yoshida, Hiroaki Fujimori, Junhui Wang, Hiromi Harada, Ylenia Suzuki, Hisanori Suzuki, Mitsuko Masutani. Rapid degradation of poly(ADP-ribose) after injection into the mouse bloodstream. Biological & pharmaceutical bulletin. 2013;36(3):462-6

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PMID: 23449331

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