NR ABJV
AU Blanquet-Grossard,F.; Sazdovitch,V.; Jean,A.; Deslys,J.P.; Dormont,D.; Hauw,J.J.; Marion,D.; Brown,P.; Cesbron,J.Y.
TI Prion protein is not detectable in dental pulp from patients with Creutzfeldt-Jakob disease
QU Journal of Dental Research 2000 Feb; 79(2): 700
PT letter
VT
Creutzfeldt-Jakob disease (CJD) occurs primarily as a sporadic disorder at an annual frequency of one case per million people and accounts for 85 to 90% of all cases. From 5 to 10% of cases are familial, and the remainder are the result of accidental iatrogenic transmissions (chiefly contaminated human growth hormone and dura mater grafts) and a new variant caused by exposure to "mad cow" disease. Infectivity and "prion" protein are detectable in the brains of patients with all forms of CJD and have also been detected in peripheral nerves in experimental models, as well as in scrapie-affected sheep (Groschup et al., 1996). Dental pulp is a richly innervated tissue of neural crest origin; thus, infectivity in the dental pulp of CJD patients could be a source of iatrogenic contamination during endodontic procedures. Experimental disease transmission in hamsters has been accomplished by inoculation of scrapie-infected brain homogenate into the dental pulp of healthy animals, and conversely, dental pulp from scrapie-infected hamsters has transmitted disease following intraperitoneal inoculation of healthy animals (Ingrosso et al., 1999).
We analyzed proteinase-K-treated homogenates from brain and dental pulps of eight patients with neuropathologically confirmed sporadic CJD. Samples were run on SDS-PAGE electrophoresis followed by Western blotting with the monoclonal 3F4-antibody (Kascsak et al., 1987). The characteristic proteinase-resistant "prion" protein (PrP res ) was present in extracts of 0.01 mg of brain tissue from all patients, but no signal was detected with the eight corresponding dental pulp homogenates prepared from approximately 10 mg of tissue (range, 1.5 to 32.7 mg). Since there is an excellent positive correlation between levels of infectivity and PrP res, any infectivity present in the dental pulp should therefore exist at a level not greater than 1/1000th that of brain tissue, an estimate consistent with data about comparative infectivity levels in neural and non-neural tissues in scrapie-infected hamsters (Kascsak et al., 1986).
In view of the fact that the average infectivity titer in the brains of humans with CJD is approximately 10^4.6 log 10 mean lethal doses (LD 50 ) per gram (Brown et al., 1994), it may be inferred that the maximum level of infectivity in dental pulp should be lower by three orders of magnitude-equal to about 40 log 10 LD 50 /g, or 0.04 log 10 LD 50 /mg. Thus, the entire 10 mg of pulp in an average tooth would contain only 0.4 log 10 LD 50 of infectivity. However, because Western blot detection of PrP res is 3 to 4 orders of magnitude less sensitive than infectivity bioassays, the risk of iatrogenic contamination by endodontic surgery cannot be entirely dismissed, and a fully convincing resolution of the question will have to await attempts to transmit disease experimentally by means of sensitive assay hosts such as primates or "humanized" transgenic mice. Until such experiments exonerate endodontal surgery from any possibility of risk, we suggest that those parts of dental instruments coming into contact with tissues from patients with known or suspected CJD be subjected to rigorous sterilization by immersion for 1 hr in 1 N NaOH, then autoclaved at 134° (if re-used), or incinerated (if disposable).
KEY WORDS: Creutzfeldt-Jakob disease, prion, dentistry, iatrogenic contamination.
ACKNOWLEDGMENT
This work was supported by grants from the Cellule de Coordination Interorganismes sur les ESSTs.
REFERENCES
Brown P, Gibbs CJ Jr, Rodgers-Johnson P, Asher DM, Sulima MP, Bacote A, et al. (1994). Human spongiform encephalopathy: the National Institutes of Health series of 300 cases of experimentally transmitted disease. Ann Neurol 35:513-529.
Groschup MH, Weiland F, Straub OC, Pfaff E (1996). Detection of scrapie agent in the peripheral nervous system of a diseased sheep. Neurobiol Dis 3:191-195.
Ingrosso L, Pisani F, Pocchiari M (1999). Transmission of the 263K scrapie strain by the dental route. J Gen Virol 80:3043-3047.
Kascsak RJ, Rubenstein R, Merz PA, Carp RI, Robakis NK, Wisniewski HM, et al. (1986). Immunological comparison of scrapie-associated fibrils isolated from animals infected with four different scrapie strains. J Virol 59:676-683.
Kascsak RJ, Rubenstein R, Merz PA, Tonna-DeMasi M, Fersko R, Carp RI, et al. (1987). Mouse polyclonal and monoclonal antibody to scrapie-associated fibril protein. J Virol 61:3688-3693.
MH Blotting, Western; Brain Chemistry; Creutzfeldt-Jakob Syndrome/*metabolism; Dental Pulp/*chemistry; Electrophoresis, Polyacrylamide Gel; Human; Iatrogenic Disease; Prions/*analysis; Risk Factors; Root Canal Therapy; Support, Non-U.S. Gov't
AD F. Blanquet-Grossard und J.-Y. Cesbron (IBL-CNRS, 1 rue du Pr. Calmette, BP447, 59021 Lille Cedex, France; jean-yves.cesbron@pasteur-lille.fr), V. Sazdovitch und J.-J. Hauw (Laboratoire de Neuropathologie, HP Pitié-Salpêtrière, 75651 Paris, Cedex 13, France), A. Jean und D. Marion (Département d'Ontologie Conservatrice-Endodontie, Faculté de Chirurgie dentaire, BP 84215, 44042 Nantes Cedex 1, France), J.-P. Deslys und D. Dormont (Laboratoire de Neurovirologie et Neuropathologie Expérimentale, CEA, BP 6, 92265 Fontenay aux Roses Cedex, France), P. Brown (Laboratory of Central Nervous System Studies, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA)
SP englisch
PO USA
OR Prion-Krankheiten 2