الفهرس 
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Abstract
Very little is known about the in vivo pathogenicity of double-walled carbon nanotubes (DWCNTs). In the present study, we compared the pulmonary toxicity of DWCNT to MWCNT-7. Rats were divided into 6 groups: untreated, vehicle, low dose DWCNT, high dose DWCNT, low dose MWCNT-7, and high dose MWCNT-7. The test materials were administered by intra-tracheal intra-pulmonary spraying (TIPS) every other day for 15 days: the low dose and high dose groups were administered final total doses of 0.25 and 0.50 mg/rat of the test material. The animals were sacrificed 1 and 6 weeks after the final TIPS administration. Six weeks after the final TIPS administration, scattered granulomas were found in the lungs of rats administered DWCNT, with DWCNT fibers present in multinucleated macrophages in the granulation tissue. DWCNT administration had no significant effect on LDH activity, ALP activity, or total protein concentration in the bronchioalveolar lavage (BALF), indicating little or no tissue damage. In contrast, MWCNT-7 administration resulted in macrophage infiltration with dense alveolar wall fibrous thickening throughout the lung and significant elevation of LDH activity, ALP activity, and total protein concentration in the BALF, indicating significant tissue damage. There was also a significant increase in the pulmonary cell PCNA index in the lungs of MWCNT treated rats, indicating repair of MWCNT-associated tissue damage. DWCNT treated rats had increased levels of CCL2 and CCL3 in the lung tissue, likely due to granuloma-associated macrophages. MWCNT treated rats had increased levels of CCL2 and CCL4 in the lung tissue. DWCNT had no effect on LDH activity or total protein concentration in the pleural cavity lavage (PL), again indicating little or no tissue damage of the pleura in DWCNT treated rats. In contrast, there was a small, but significant, increase in protein concentration in the PL supernatant in MWCNT treated rats and an increase in the visceral mesothelial cell PCNA index. Finally, MWCNT treated rats, but not DWCNT treated rats, had elevated levels of 8-OHdG DNA adducts in the lung, indicating that MWCNT exposure resulted in DNA damage. Respirable foreign-body carcinogens must cause both tissue damage and the generation of DNA damaging agents, generally reactive oxygen and nitrogen species. This results in reactive oxidant-mediated damage of the DNA of proliferating cells, allowing replication of damaged DNA before the damage can be repaired, and fixation of mutations in the genome of daughter cells. DWCNT administration did not cause tissue damage, tissue repair, or DNA damage. On the other hand, administration of MWCNT-7, a known carcinogen to the lung of rats, caused tissue damage, tissue repair, and DNA damage. In conclusion, our data indicate that MWCNT-7 has higher pulmonary and pleural toxicity than DWCNT and suggest that MWCNT-7 has higher carcinogenic potential than DWCNT.