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BrdU screening - a short-time test for reliable prediction of carcinogenicity for MWCNT

: Hackbarth, Anja; Schaudien, Dirk; Bellmann, Bernd; Ernst, Heinrich; Leonhardt, Albrecht; Heinrich, Uwe; Rittinghausen, Susanne

The Toxicologist 53 (2014), No.1, pp.527-528, PS 2003
ISSN: 0731-9193
Society of Toxicology (Annual Meeting) <53, 2014, Phoenix/Ariz.>
Fraunhofer ITEM ()

Since the discovery of the excellent features of MWCNT, there has been an increase in potential applications, despite the fact that they have been discussed to have a toxic potential depending on their length and fiber-like shape. For this reason, potential adverse biological effects of MWCNT have been investigated in vivo (rat) in a project funded by the German BMBF (contract No. 03X0109A). Tailor-made MWCNT with different lengths and diameters were produced, suspended in artificial lung medium and injected intraperitoneally in rats in two dose groups (low: 1x109 WHO fibers; high: 5x109 WHO fibers) in a BrdU screening test (MWCNT 1, 2, 3) and a carcinogenicity study (MWCNT 1, 2, 3, 3a).
Long amosite asbestos (0.1x109 WHO fibers) served as positive control, ground MWCNT and Printex 90 (5 mg/rat) as negative control. Suspension and length/ diameter distribution were measured in SEM.
Proliferation of cells in the diaphragmatic peritoneum was investigated as a shorttime screening test 3 and 6 months after i.p. injection of fibers in rats, using the BrdU method and measurement of peritoneal thickness. Furthermore, animal mortality and tumor development were monitored over two years in a carcinogenicity study. There was a time-independent significant increase in cell proliferation after injection of MWCNT 1(high) (L=7.9 m; D=0.037 m), MWCNT 2(low/high) (L=10.24 m; D=0.04 m), and MWCNT 3(low/high) (L=8.57 m; D=0.085m), like after exposure to long amosite asbestos (L=13.95 m; D=0.39 m) as positive control. MWCNT 2(high) and 3(low/high) induced significant dose-dependent thickening of the peritoneum after i.p. injection, independently of time.
In the carcinogenicity study, MWCNT 2, 3 and 3a (L=9.3 m; D=0.062 m) showed a higher mesothelioma incidence than MWCNT 1.
In conclusion, some MWCNT (MWCNT 2, 3) mediate enhanced proliferation of peritoneal cells in the diaphragm in rats, which may result in mesothelioma development.