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

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

Naunyn-Schmiedebergs archives of pharmacology 387 (2014), Supplement 1, pp.S46, A180
ISSN: 0028-1298
ISSN: 1432-1912
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie (Annual Meeting) <80, 2014, Hannover>
Journal Article, Conference Paper
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 mm; D=0.037 mm), MWCNT 2(low/high) (L=10.24 mm; D=0.04 mm), and MWCNT 3(low/high) (L=8.57 mm; D=0.085 mm), like after exposure to long amosite asbestos (L=13.95 mm; D=0.39 mm) 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 mm; D=0.062 mm) 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.