Combined drug and surgery treatment of plutonium-contaminated wounds: indications obtained using a rodent model.
There is an important requirement following accidental actinide contamination of wounds to limit the dissemination and retention of such alpha-emitting radionuclides. To reduce wound and systemic contamination, treatment approaches include chelation therapy with or without wound excision. However, it has been hypothesized that wound excision could lead to increased contaminant release and systemic organ retention. This study in the rat addresses this question. Anesthetized rats were contaminated with plutonium nitrate following wounding by deep incision of hind leg muscle. Excision of tissue at the contaminated site was performed 7 d later with or without Diethylene Triamine Pentaacetic Acid (DTPA) treatment (30 μmol kg⁻¹ i.v.). Pu urinary excretion was then measured for a further 3 d, and animals were euthanized at 14 d after contamination. Tissue samples were evaluated for Pu activity and histology. At 7 d after contamination, around 50% of the initial activity remained at the wound site. An average of 16% of this activity was then removed by surgery. Surgery alone resulted in increased urinary excretion, suggesting release from the wound site, but no subsequent increases in organ retention (bone, liver) were observed at 14 d. Indeed, organ Pu activity was slightly reduced. The combination of surgery and DTPA or DTPA treatment alone was much more effective than excision alone as shown by the markedly increased urinary Pu excretion and decreased tissue levels. This is the first report in an experimental rodent model of resection of Pu-contaminated wound. Urinary excretion data provide evidence for the release of activity as a result of surgery, but this does not appear to lead to further Pu organ retention. However, a combination of prior DTPA treatment with wound excision is particularly effective.
*Laboratoire de RadioToxicologie, CEA/DSV/iRCM, Bruyères le Châtel, 91297 ARPAJON, France.
Nina M
NM
Griffiths
Sylvie
S
Coudert
Jean Claude
JC
Wilk
Daniel
D
Renault
Jaime F
JF
Angulo
Anne
A
Van der Meeren
D000818:Animals; D004195:Disease Models, Animal; D006657:Histones / Q000378:metabolism; D008297:Male; D004369:Pentetic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D010750:Phosphoproteins / Q000378:metabolism; D011005:Plutonium / Q000633:toxicity* / Q000652:urine; D018788:Radioactive Hazard Release; D051381:Rats; D017207:Rats, Sprague-Dawley; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000601:surgery*
D006657:Histones; D010750:Phosphoproteins; C577575:gamma-H2AX protein, rat; D011005:Plutonium; D004369:Pentetic Acid