Tracheal explant

Chopra, D. P., and Joiakim, A. P. (1991). Differences in lectin binding in squamous metaplasia induced by benzo(a)pyrene and vitamin A deficiency in hamster tracheal explants. 

NT193 Wang, R. D., H. Tai, C. Xie, X. Wang, ]. L. Wright, and A. Churg. Cigarette smoke produces airway wall remodeh ing in rat tracheal explants. Am J Respir Crit Care Med 2003 168(10) 1232-1236. 

Steele, V.E., IVIarchok, A.C., and Nettensheim, P. (1979). Oncogenic transformation in epithelial cell lines derived from tracheal explants exposed in vitro to N-methyl-N-nitro N nitrosoguanine, Cancer Res. 39,3805. 

Hydrogen peroxide induced squamous metaplasia in hamster tracheal explants at concentrations of 50-100 pmol/L, while cytotoxicity was observed only at concentrations... 

Hobson J, Gilks B, Wright J, et al. 1988. Direct enhancement by cigarette smoke of asbestos fiber penetration and asbestos-induced epithelial proliferation in rat tracheal explants. J Natl Cancer Inst 80 518-521. 

Holtz G, Bresnick E. 1988. Ascorbic acid inhibits the squamous metaplasia that results from treatment of tracheal explants with asbestos or benzo[a]pyrene-coated asbestos. Cancer Lett 42 23-28. 

Cultured fetal hamster tracheal explants were exposed to two concentrations each of... 

Interactions between selected noncarcinogenic PAHs and carcinogenic benzo[a]pyrene have also been documented to reduce the carcinogenic potential of benzo[a]pyrene in animals. Benzo[a]fluoranthene, benzo[k]fluoranthene, chrysene, perylene, and a mixture of anthracene, phenanthracene, and pyrene significantly inhibited benzo[a]pyrene-induced injection-site sarcomas. However, other PAHs including anthracene, benzo[g,h,i]perylene, fluorene, and indeno[1,2,3-c,d]pyrene had no antagonistic effects (Falk et al. 1964). Coexposure of tracheal explants to benzo[e]pyrene and benzo[a]pyrene resulted in an increased incidence of tracheal epithelial sarcomas over that seen with either PAH alone (Topping et al. 1981). Phenanthrene administration with benzo[a]pyrene decreased the DNA adduct formation in mice (Rice et al. 1984). 

Tracheal explants Finely minced trachea cultured in vitro from which biochemicals including procollagen can be released. 

Cigarette smoke pre-treatment of rat tracheal explants increased binding of amosite particles to the epithelial surface (Churg et al. 1997b). Ozone (0.01 to 1.0 ppm for 10 min) enhanced the uptake of UICC amosite in a dose-response fashion (Churg et al. 1996). 

By electron microscopy, Churg et al. (1998) found TiOj particles in the epithelial cells of rat tracheal explants cultured in Dulbecco s modified Eagle s medium. The volume proportion of both fine (120 nm) and ultrafine (21 nm) particles in the epithelium increased from 3 to 7 days it was greater for ultrafine particles at 3 days but was greater for fine particles at 7 days. Ultrafine particles appeared to enter the epithelium faster, and once in the epithelium, a greater proportion of them was translocated to the subepithelial space compared with fine particles. However, if it was assumed that the volume proportion was representative of particle number, the number of particles reaching the interstitial space was directly proportional to the number applied, i.e., overall, there was no preferential transport from lumen to interstitium by size. 

As a contribution to the byssinotic effects of cotton seed Duckett and Kennedy (1983) exposed rabbit tracheal explants to gossypol and found a dose dependent (10" M, 5x10 M, 10" M) inhibition of ciliary function. Mitochondria appeared swollen and cristae were disrupted. 

Animal studies to date have failed to show consistent evidence of an anticancer action of vitamin C. Holtz and Bresnick (1988) reported that ascorbic acid inhibited the squamous metaplasia that results from the treatment of tracheal explants with asbestos or benzo(a)pyrene-coated asbestos. Liehr et al. (1989) found that vitamin C could inhibit estrogen-induced renal carcinogenesis in male ham-... 

Table 1 Types of Mineral Particles Reported to be Taken Up by Pulmonary Tracheobronchial and Alveolar Epithelial Cells in Experimental In Vivo and Tracheal Explant Systems...

A different line of evidence for the idea that failure to remove particles from the lung leads to epithelial uptake comes from experiments using tracheal explants. Tracheal explants are, for practical purposes, free of inflammatory cells. If such explants are briefly exposed to a suspension of dust particles, the particles... 

Figure 1 Micrograph of a rat tracheal explant The explant was initially exposed to amosite asbestos for 1 hr, then maintained in air organ eulture for 7 days, and fixed and processed for histological assessment. Note the adherent mass of fibers on the apieal epithelial surface some fibers have been taken up by the epithelium and some (arrows) have been translocated to the connective tissue layer beneath the epithelium. Cartilage is visible at the bottom of the field. Space between mass of fibers and apical surface is an artifact of cutting direction. (From Ref 161.)...

Little information is available about differences in particle uptake as a function of either anatomical location within the lung or as a function of cell type. In the mouse, all types of conducting airway cells, except mucous cells, phagocytosed 5-nm-iron oxide particles administered by inhalation (72,73). The iron oxide particles were translocated through the cell to the interstitium, and this phenomenon appeared to occur primarily in ciliated cells. In human bronchial explants, the ciliated cells took up both asbestos and glass fibers (71), but uptake occurred primarily in areas with relatively few cilia, apparently because areas with numerous actively beating cilia tended to move particles away from the cell surfaces. In hamster tracheal explants, there was a similar effect for long, but not short, fibers of both chrysotile and crocidolite. 

We (116) have recently used rat tracheal explants in an attempt to examine this problem in a simpler system. Explants were exposed to fine (0.12-pm) or ultrafine (0.021-pm) titanium dioxide at a particle number ratio of 1 200, and maintained in organ culture. Particle uptake was determined morphometrically... 

In tracheal explants, the basal level of amosite asbestos uptake can be decreased by adding catalase, a scavenger of hydrogen peroxide, to the dust suspension, or by preincubating the dust with the iron chelator, deferoxamine (124), a chelator that prevents the reaction of iron with hydrogen peroxide to form a hydroxyl radical (6). The decreases in particle uptake are scavenger-chelator dose-dependent, but uptake cannot be reduced below about one-third to one-half the basal level (124). Conversely, uptake can be increased if amosite asbestos or titanium dioxide particles are preincubated with iron salt solutions to increase surface iron before they are applied to the explants (125). 

Figure 2 Effects of cigarette smoke and scavengers of active oxygen species on the uptake of titanium dioxide (Ti) in a rat tracheal explant system. Explants were exposed to smoke or air for 10 min and then submerged for 1 hr in a suspension of titanium dioxide, followed by 7 days of air organ culture. In some experiments, catalase (CAT) or inactivated catalase (CATI) was added to the dust suspension in other experiments the dust was incubated overnight in deferoxamine (DFX). Smoke (S) markedly enhanced titanium dioxide uptake, and both catalase and deferoxamine completely abolished the smoke effect, suggesting that the hydrogen peroxide and the hydroxyl radical are involved. Inactivated catalase was not protective. (From Ref 53.)...

Direct observation indicates that exposure of tracheal explants to a mineral dust suspension results in visible binding of the particles to the apical membrane of the tracheal epithelial cells (see Fig. 1). The same process probably occurs with alveolar epithelium. However, little is known about how particles bond to epithelial cells. 

Churg A, Wright J, Stevens B. Comparison of the uptake of fine and ultrafine titanium dioxide in a tracheal explant system. Am J Physiol 1998 274 281-286. 

Churg A, Hobson J, Berean K, Wright J. Scavengers of active oxygen species prevent cigarette smoke induced asbestos fiber penetration in rat tracheal explants. Am J Pathol 1989 135 599-603. 

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