Telomere length and genotoxicity in the lung of rats following intragastric exposure to food-grade titanium dioxide and vegetable carbon particles

被引:33
作者
Jensen, Ditte Marie [1 ]
Lohr, Mille [1 ]
Sheykhzade, Majid [2 ]
Lykkesfeldt, Jens [3 ]
Wils, Regitze Solling [2 ]
Loft, Steffen [1 ]
Moller, Peter [1 ]
机构
[1] Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Sect Environm Hlth, DK-1870 Frederiksberg C, Denmark
[2] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, Sect Mol & Cellular Pharmacol, DK-1870 Frederiksberg C, Denmark
[3] Univ Copenhagen, Fac Hlth & Med Sci, Dept Vet & Anim Sci, Expt Anim Models, DK-1870 Frederiksberg C, Denmark
关键词
OXIDATIVELY DAMAGED DNA; DIESEL EXHAUST PARTICLES; SHORT-TERM EXPOSURE; AIR-POLLUTION; EPITHELIAL-CELLS; VASOMOTOR DYSFUNCTION; VASCULAR DYSFUNCTION; PARTICULATE MATTER; PULMONARY EXPOSURE; GENE-EXPRESSION;
D O I
10.1093/mutage/gez003
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Vegetable carbon (E153) and titanium dioxide (E171) are widely used as black and white food colour additives. The aim of this study was to assess gastrointestinal tight junction and systemic genotoxic effects in rats following exposure to E153 and E171 for 10 weeks by oral gavage once a week. The expression of tight junction proteins was assessed in intestinal tissues. Levels of DNA strand breaks, oxidatively damaged DNA and telomere length were assessed in secondary organs. Hydrodynamic suspensions of E153 and E173 indicated mean particles sizes of 230 and 270 nm, respectively, and only E153 gave rise to intracellular production of reactive oxygen species in colon epithelial (Caco-2) cells. Rats exposed to E153 (6.4 mg/kg/week) or E171 (500 mg/kg/week) had decreased gene expression of the tight junction protein TJP1 (P < 0.05). E153 (6.4 mg/kg/week) also decreased OCLN (P < 0.05) in the colon and occludin protein expression in the small intestine (P < 0.05). Furthermore, E153 or E171 exposed rats had shorter telomeres in the lung (P < 0.05). Plasma from particle-exposed rats also produced telomere shortening in cultured lung epithelial cells. There were unaltered levels of oxidatively damaged DNA in the liver and lung and no changes in the DNA repair activity of oxidatively damaged DNA in the lung. Altogether, these results indicate that intragastric exposure to E153 and E171 is associated with reduced tight junction protein expression in the intestinal barrier and telomere length shortening in the lung in rats.
引用
收藏
页码:203 / 214
页数:12
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