Determination of cocarcinogenic activity of benzo[e]pyrene for respiratory tract mucosa

Topping, Douglas C.; Martin, Donald H.; Nettesheim, Paul

doi:10.1016/0304-3835(81)90097-5

Cited by 14 publications

(12 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Insertion of chrysotile asbestos into rodent tracheal grafts previously exposed to a chemical initiator results in the development of tumors arising from the tracheal epithelium. In contrast, fibers alone do not induce tumors (4).…”

mentioning

confidence: 99%

Hydrolysis of inositol phospholipids precedes cellular proliferation in asbestos-stimulated tracheobronchial epithelial cells.

Sesko

Cabot

Mossman

1990

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Metabolism of inositol phospholipids and phosphatidylcholine was investigated in tracheobronchial epithelial cells exposed to mitogenic concentrations of crocidolite asbestos. Alterations in levels of diacylglycerol, the endogenous activator of protein kinase C, and inositol polyphosphates, presumed mobilizers of intracellular calcium, were examined. Occupational exposure to asbestos results in development of bronchogenic carcinoma, mesothelioma, and asbestosis (1). The pathogenesis of carcinoma caused by asbestos has been studied experimentally in tracheobronchial epithelial cells and organ cultures. Results suggest that asbestos is a classical tumor promoter in the development of bronchogenic carcinoma. For example, many of the effects reported in mouse skin cells exposed to tumor-promoting phorbol esters (2) occur in tracheobronchial epithelial cells exposed to asbestos (3). Additionally, asbestos acts as a tumor promoter in a "two-stage" model of carcinogenesis. Insertion of chrysotile asbestos into rodent tracheal grafts previously exposed to a chemical initiator results in the development of tumors arising from the tracheal epithelium. In contrast, fibers alone do not induce tumors (4).Many of the morphological and biochemical changes expressed in cells exposed to soluble tumor promoters such as phorbol 12-myristate 13-acetate (PMA) occur after direct interaction of PMA with calcium-and phospholipiddependent protein kinase C (PKC) (5), an enzyme implicated in cellular growth control. For example, dramatic morphological changes have been seen in rat fibroblasts that overproduce a transfected isoform of PKC (6). Recent work from this laboratory implicates PKC in crocidolite asbestosinduced proliferation of hamster tracheal epithelial (HTE) cells, a cell type giving rise to bronchogenic tumors. For example, asbestos-stimulated induction of ornithine decarboxylase is reduced by inhibitors of PKC (7). Because it is unlikely that soluble asbestos fibers bind directly to PKC as do the lipophilic phorbol esters, we sought to investigate other plausible mechanisms whereby asbestos fibers could initiate PKC-mediated proliferation. In this report, we present evidence that diacylglycerol (acyl2Gro), the endogenous activator of PKC, is produced upon hydrolysis of inositol phospholipids in crocidolite-stimulated HTE cells. MATERIALS AND METHODSChemicals. Union Internationale Contre le Cancer reference samples of crocidolite [(Na2Fe2Fe3+(Si8022)(0H)2] asbestos were used in these studies. Riebeckite (a nonfibrous particle) and glass beads (8) were used as negative controls to determine whether fibrous geometry was critical for inducing altered lipid metabolism. Physiochemical characterization and size dimensions of fibers and particles have been pub- (0.5 ,uCi/ml, Ci/mmol; 1 Ci = 37 GBq) for 24 hr and at confluency were incubated briefly (1 hr) with unlabeled medium. Agents (phospholipase C, PMA, or asbestos) then were added in fresh serum-free medium, and exposures were continued for 10-240 min. Next, cultures...

show abstract

mentioning

confidence: 99%

Hydrolysis of inositol phospholipids precedes cellular proliferation in asbestos-stimulated tracheobronchial epithelial cells.

Sesko

Cabot

Mossman

1990

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…In experimental models using rodent tracheal grafts, asbestos appears to act primarily as a cocarcinogen (11) or tumor promoter (12), perhaps by facilitating the uptake, metabolism, and/or DNA binding of chemical carcinogens (13). Alternatively, asbestos causes chronic inflammation and may foster the development of tracheobronchial neoplasms by acting as a mitogen in a manner similar to the tumor promoter phorbol 12-myristate 13-acetate ("12-O-tetradecanoylphorbol 13-acetate," TPA) (1).…”

mentioning

confidence: 99%

Persistent induction of c-fos and c-jun expression by asbestos.

Heintz

Janssen

Mossman

1993

Proc. Natl. Acad. Sci. U.S.A.

188

View full text Add to dashboard Cite

To investigate the mechanisms of asbestos-induced carcinogenesis, expression of c-fos and c-jun protooncogenes was examined in rat pleural mesothelial cells and hamster tracheal epithelial cells after exposure to crocidolite or chrysotile asbestos. In contrast to phorbol 12-myristate 13-acetate, which induces rapid and transient increases in c-fos and c-jun mRNA, asbestos causes 2- to 5-fold increases in c-fos and c-jun mRNA that persist for at least 24 hr in mesothelial cells. The induction of c-fos and c-jun mRNA by asbestos in mesothelial cells is dose-dependent and is most pronounced with crocidolite, the type of asbestos most pathogenic in the causation of pleural mesothelioma. Induction of c-jun gene expression by asbestos occurs in tracheal epithelial cells but is not accompanied by a corresponding induction of c-fos gene expression. In both cell types, asbestos induces increases in protein factors that bind specifically to the DNA sites that mediate gene expression by the AP-1 family of transcription factors. The persistent induction of AP-1 transcription factors by asbestos suggests a model of asbestos-induced carcinogenesis involving chronic stimulation of cell proliferation through activation of the early response gene pathway that includes c-jun and/or c-fos.

show abstract

“…Therefore, the preadsorption of P A H on inorganic solids plays a role in the distribution and the availability of these PAH in biological medium, which also explains the results of the animal experiments (3,4) where a great percentage of bronchopulmonary cancers is observed when the P A H is introduced as preadsorbed on a basic, inorganic solid by intratracheal injection.…”

Section: Discussionmentioning

confidence: 81%

Thermodynamic aspects in the adsorption of polynuclear aromatic hydrocarbons on chrysotile and silica – possible relation to synergistic effects in lung toxicity

Fournier¹,

Fubini²,

Bolis³

et al. 1989

Can. J. Chem.

View full text Add to dashboard Cite

. 67,289 (1989).This study is to compare the adsorption of phenanthrene -a polynuclear aromatic hydrocarbon -(apolar molecule) and water (polar molecule) on chrysotile, a mainly ionic solid and on one silica (Aerosil), a covalent solid. The adsorption of water shows that the adsorption capacity and the interaction energies are much higher for chrysotile than for silica. With phenanthrene, the adsorption mechanism on these two materials is very different: on chrysotile-a solid with a surface having a basic character -there is a multilayer adsorption, with lateral interactions between PAH molecules vertically oriented with regard to solid surface, whereas on silica (acidic solid), the PAH molecules are adsorbed flat and form only one layer. Chrysotile turns out to be a much more powerful adsorbent than silica towards both polar molecules and apolar molecules. The calorimetric data concerning the adsorption of phenanthrene on chrysotile in xylene reveal three thermal stages, showing the influence of preadsorbed water and solvent and permit to propose a model of adsorption mechanism. The formation of multilayers of phenanthrene on chrysotile converts its marked hydrophilic surface into a hydrophobic one which may act as a carrier of organic molecules and slowly release them into the biological medium. These phenomena may provide a possible interpretation for some synergistic effects concerning lung cancers observed after asbestos and cigarette-smoke exposure.Key words: adsorption, phenanthrene, chrysotile, silica, water.JEANINE FOURNIER, BICE FUBINI, VERA BOLIS et HENRI PEZERAT. Can. J. Chem. 67,289 (1989).La comparaison des propriCtCs d'adsorption d'un solide ionique, le chrysotile avec celles d'un solide covalent, une silice (ACrosil), est fondCe sur 1'Ctude de l'adsorption d'un hydrocarbure polycyclique aromatique, le phknanthrkne (molCcule apolaire) dans le xylkne et d'une molCcule polaire a 1'Ctat gazeux, l'eau. L'adsorption de l'eau montre que la capacite' d'adsorption et 1'Cnergie d'interaction (solide-H20) sont beaucoup plus importantes dans le cas du chrysotile que dans le cas de la silice. L'adsorption du phenanthrkne differe selon le matCriau CtudiC. En effet, pour le chrysotile dont la surface prCsente un caractkre basique, les isothermes rCvklent une adsorption en multicouches avec la presence d'interactions IatCrales entre les moltcules adsorbies, ces molCcules Ctant orientCes verticalement par rapport la surface. Par contre, pour la silice, seule une monocouche est formCe avec des molCcules adsorbtes 2 plat. Tous ces rCsultats font apparaitre que le chrysotile a une capacitC d'adsorption pour le phknanthrkne et pour l'eau trks supCrieure a celle de la silice. La presence de trois Ctapes thermiques lors de I'adsorption du phinanthrkne sur le chrysotile rCvkle l'influence du solvant et de l'eau prCadsorbCe. Ces donnCes calorimttriques permettant de proposer un modkle de mecanisme d'adsorption. La surface du chrysotile, initialement hydrophile devient hydrophobe du fait de la prksence de multicouches de ...

show abstract

Determination of cocarcinogenic activity of benzo[e]pyrene for respiratory tract mucosa

Cited by 14 publications

References 9 publications

Hydrolysis of inositol phospholipids precedes cellular proliferation in asbestos-stimulated tracheobronchial epithelial cells.

Hydrolysis of inositol phospholipids precedes cellular proliferation in asbestos-stimulated tracheobronchial epithelial cells.

Persistent induction of c-fos and c-jun expression by asbestos.

Thermodynamic aspects in the adsorption of polynuclear aromatic hydrocarbons on chrysotile and silica – possible relation to synergistic effects in lung toxicity

Contact Info

Product

Resources

About