Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “EPITHELIUM”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1990

Accessibility and possibility of elimination of breast epithelium: the theoretical possibility of preventing breast carcinoma through destruction of the epithelium of origin.

Two characteristics of breast biology appear to constitute weak points in the fight against breast carcinoma. First, the epithelium from which breast carcinoma arises is of relatively easy accessibility, as it lines cavities which are in close communication with the outside. Second, the elimination of breast epithelium can be tolerated by the organism. Theoretically, breast carcinoma may be prevented by destroying breast epithelium through the injection of an agent into the ductal orifices at the nipple. This strategy appears relatively easy to perform in comparison with conventional strategies, which have not given reliable results. Therefore the possibility presented here should not be neglected.

Breast↗
PubMed2001

Betaine aids in the osmoregulation of duodenal epithelium of broiler chicks, and affects the movement of water across the small intestinal epithelium in vitro.

In Experiment 1, the water holding capacity of broiler chick intestinal tissue was studied in vitro. The chicks were fed with corn-based diets with or without a 0.2% betaine supplementation in the drinking water. Slices from duodenum and jejunum were incubated in iso-osmotic (300 mM) or hyperosmotic saline (600 mM) with or without 10 mM betaine. The water volume of tissue slices was studied by adding tritiated water in the incubation medium while [14C]inulin was used to correct for the adherent water. After 30 min of incubation, by which time the steady-state of tritium influx had been achieved, the 3H and 14C-activities of the tissue slices were measured. The ileal and duodenal tissues incubated in the hyperosmotic saline accumulated less tritium than those incubated in iso-osmotic saline. Duodenal slices incubated in hyperosmotic saline with the presence of betaine showed a tritium content similar to slices incubated in iso-osmotic saline. The data suggest that the presence of betaine helped the duodenal, but not jejunal, epithelium to maintain water balance in hyperosmotic conditions. The dietary betaine supplementation diminished the differences between the incubation treatments in duodenal, but not in ileal tissue. In Experiment 2, the same double labeling method, but with shorter incubation times, was used to assess the rate of water flux from the incubation medium to duodenal or jejunal slices. The dietary treatments (as in Experiment 1) had little effect on the results. Betaine in the hyperosmotic saline significantly decreased the rate of tritium accumulation into the tissue slices, indicating that betaine slowed down the influx of water to the epithelium. We suggest that betaine affects the movement of water across the intestinal epithelium and has a role in the osmoregulation of small intestine of broiler chicks.

Animals↗
PubMed1988

Distribution of Langerhans cells in clinically healthy human gingival epithelium with special emphasis on junctional epithelium.

Twenty-one biopsies of clinically healthy marginal gingiva from children, who performed conventional oral hygiene but received no additional professional prophylaxis, were studied in order to obtain information on distribution and density of Langerhans cells (LC) in the oral gingival epithelium (OGE), the sulcular epithelium (SE) and the junctional epithelium (JE). A simple freeze-separation technique was found to create acceptable histomorphology of JE in specimens obtained adherent to teeth, while partially and non-adherent ones were rejected. The majority of LC in OGE were highly dendritic and stained intensively with OKT6 monoclonal antibodies. The distribution was network-like with a density of 21.0 +/- 3.2 LC/0.1 mm2 cross-sectional epithelial area. A similar although less dense distribution was found in SE (8.6 +/- 3.0 LC/0.1 mm2). These observations confirm previous findings. In JE 2 groups of LC were identified: 1) Weakly stained LC with very few and short dendrites distributed in a scattered way (2.8 +/- 1.4 LC/0.1 mm2) in the apical three-fourths of JE in most specimens. Present evidence suggests that these cells might be immature cells of Langerhans lineage. 2) Clusters of LC (9.4 +/- 2.9 LC/0.1 mm2) with dendrites of moderate lengths and numbers and a varied fluorescence intensity; they were found in a few specimens in the coronal one-fourth of JE and at the border zone to SE. Such clusters might represent genuine variation in the distribution of LC or reactions to initial/early plaque formation.

Adolescent↗
PubMed1992

[Krypton laser therapy. Use in secondary serous detachment of the retinal pigment epithelium and in multiple idiopathic serous detachments of the retinal pigment epithelium].

Two variants of serious detachments of the retinal pigment epithelium (RPE) are demonstrated with reports of typical cases: (1) secondary serous detachment of the RPE; (2) idiopathic serous detachment of the RPE (pigment epithelium detachment not associated with any other retinal or choroidal disease). Fluorescein angiographic criteria for differential diagnosis and the resulting different techniques of krypton laser coagulation are portrayed: (a) focal krypton laser coagulation of the total area of the pigment epithelium detachment; (b) circular, one-row laser coagulation at the detachment borders. The advantages of circular, one-row laser coagulation of idiopathic serous RPE detachment over coagulation of the total area of the RPE detachment are described: first, these are fewer scotomas following coagulation; second, fewer laser foci are required; and third, the risk of subretinal bleeding is lower. These findings emphasize the efficiency of circular, one-row laser coagulation at the detachment borders in the treatment of idiopathic serous RPE detachments.

Adult↗
PubMed1993

A tumor promoter-resistant subpopulation of progenitor cells is larger in limbal epithelium than in corneal epithelium.

PURPOSE: In the epidermis, proliferative basal cells can be divided into two subpopulations according to their response to phorbol ester tumor promoters. The tumor promoter-sensitive subpopulation ceases mitosis and initiates terminal differentiation and, thus, represents more differentiated transient amplifying cells. In contrast, the tumor promoter-resistant subpopulation that continues to proliferate may be the target of neoplastic transformation by chemical carcinogens and may contain stem cells. Based on this concept, we examined the differential response of stem cell-containing limbal epithelium and transient amplifying cell-containing corneal epithelium to phorbol 12-myristate 13-acetate (PMA) treatment. METHODS: A reported serum-free clonal growth assay was used. The mitogenic response was measured by colony-forming efficiency (CFE), colony size, bromodeoxyuridine (BrdU) labeling index; the differentiation was assessed by colony morphology, AE-5 monoclonal antibody staining. RESULTS: The addition of PMA dose dependently inhibited the clonal proliferation of both limbal and corneal epithelial cultures with respect to CFE, colony size, and BrdU labeling index, suggesting that both cultures contain PMA-sensitive subpopulations. Nevertheless, the magnitudes of a decrease in CFE and colony size in peripheral corneal cultures were significantly greater than those in limbal cultures, indicating that the size of the PMA-resistant subpopulation is larger in the limbal epithelium. The inhibitory effect of PMA on clonal proliferation was partially reversible upon its early withdrawal, indicating that its inhibitory effect is continuous and coupled with progressive differentiation of progenitor cells in this culture system. CONCLUSION: These results further suggest that the cell cycle length of progenitor cells correlates with the mitogenic pathway mediated via calcium- and phospholipid-dependent protein kinase C, the receptor inhibited by prolonged treatment of phorbol ester tumor promoters.

Animals↗
PubMed1987

Genesis of cilia and microvilli of rat nasal epithelia during prenatal development. III. Respiratory epithelium surface, including a comparison with the surface of the olfactory epithelium.

During prenatal development the respiratory epithelium surface of the rat's nasal septum underwent the following changes. At intra-uterine day E14 there was a transformation from State I, cells with primary cilia only, to cells which also had microvilli (Stage II). Anterior parts of the nasal septum retained microvilli throughout further development. Posteriorly, centriole multiplication (Stage III) and formation of shafts of secondary cilia (Stage IV) occurred from around E16 and E18 onwards, respectively. From E18 to E20 numbers of cells with cilia increased at an overall rate of about 6 X 10(6) cells/cm2/day. Respiratory cilia and microvilli grew, on average, by about 0.3 micron/day and 0.1 micron/day, respectively. At Stage V, beginning around E19, the cilia became aligned within cells and, at Stage VI, beginning around E21, became synchronised between cells. Respiratory ciliogenesis in the nose is most precocious near the olfactory epithelium. The formation of respiratory cilia starts after that of olfactory cilia. However, unlike olfactory epithelium surfaces those of ciliated respiratory epithelia resembled those of adults around birth.

Animals↗
PubMed1977

[Characteristics of the follicular epithelium in the fishes with demersal roe. Concerning the classification of unilaminate monomorphous follicular epithelium of the vertebrates].

Follicular epithelium of Hemichromis during the periods of small and slow oocyte growth changes from flattened prismatic into high prismatic; during the periods of fast oocyte growth, the follicular epithelial cells undergo secretory specialization. Secretion is of apocrine type and forms the second oocyte tunica. According to the literature data analyzed and the author's investigation, in the development of unilaminate monomorphous follicular epithelii, it should be distinguished: a) period of primary transformation with characteristic intensive proliferation of epithelial cells, their morphologic transformation, upward growth of epithelium and increase of its physiological activity; b) period of secondary transformation either at the expense of secondary follicular epithelial flattening, or by means of secretory specialization of its cells. It is suggested to name unilaminate monomorphous follicular epithelii in vertebrates according to their construction at the end of the primary and by the character of the secondary transformation. Thus, follicular epithelium of Hemichromis can be defined as highly prismatic with secondary specialization.

Animals↗
PubMed2001

Pigment epithelium-derived factor supports normal Müller cell development and glutamine synthetase expression after removal of the retinal pigment epithelium.

In conditions in which the retinal pigment epithelium (RPE) is dystrophic, carries a genetic mutation, or is removed physically, Müller cells undergo degenerative changes that contribute to the retinal pathology. We previously demonstrated that pigment epithelium-derived factor (PEDF), a glycoprotein secreted by the RPE cells with neuroprotective and differentiation properties, protects against photoreceptor degeneration induced by RPE removal. The purpose of the present study was to analyze the putative gliosupportive activity of PEDF on Müller cells of RPE-deprived retinas and assess whether protection of Müller cells was correlated with improved photoreceptor outer segment assembly. Eyes were dissected from Xenopus laevis tadpoles, and the RPE was removed before culturing in medium containing purified PEDF, PEDF plus anti-PEDF, or medium alone. Control eyes matured with an adherent RPE or in medium containing PEDF plus nonimmune serum. Müller cell ultrastructure was examined. Glial fibrillary acidic protein (GFAP) and glutamine synthetase were localized immunocytochemically, and the corresponding protein levels were quantified. In control retinas, Müller cells were structurally intact and formed adherens junctions with neighboring photoreceptors. In addition, they did not express GFAP, whereas glutamine synthetase expression was high. RPE removal dramatically altered the ultrastructure and biosynthetic activity of Müller cells; Müller cells failed to form adherens junctions with photoreceptors and glutamine synthetase expression was suppressed. PEDF prevented the degenerative glial response; Müller cells were ultrastructurally normal and formed junctional complexes with photoreceptors. PEDF also preserved the expression of glutamine synthetase at near-normal levels. The morphogenetic effects of PEDF were blocked by the anti-PEDF antibody. Our study documents the glioprotective effects of PEDF and suggests that maintenance of the proper Müller cell ultrastructure and expression of glutamine synthetase may be necessary to support the proper assembly of photoreceptor outer segments.

Animals↗
PubMed2006

Pigment epithelium-derived factor protects retinal pigment epithelium from oxidant-mediated barrier dysfunction.

Retinal pigment epithelium (RPE) cells form a monolayer at the blood-retina barrier between the retina and choriocapillaries. The barrier function may be damaged by multiple stresses to the cell, including the repeated exposure to oxidants that are generated by photoreceptor cell turnover. The purpose of our study was to document the protective effect of pigment epithelium-derived factor (PEDF), a tropic factor produced by the RPE, on H(2)O(2)-induced RPE barrier dysfunction. When assayed by a FITC-labeled dextran transepithelial flux, the increased permeability of the RPE barrier (induced by H(2)O(2)) was prevented by PEDF pretreatment. To further explore the mechanism leading to this permeability change, we investigated the distribution of cytoskeleton and junctional proteins. The redistribution of the two junctional proteins occludin, and N-cadherin and actin reorganization in RPE, induced by H(2)O(2), can be prevented by PEDF pretreatment. PEDF can also prevent H(2)O(2)-induced stress kinase p38/27-kDa heat shock protein signaling which is known to mediate actin rearrangement. These findings indicated that PEDF can stabilize actin, maintain normal membrane occludin and N-cadherin structure, and preserve the barrier function of RPE cells against oxidative stress.

Actins↗
PubMed2004

Pigment epithelium-derived factor in the monkey retinal pigment epithelium and interphotoreceptor matrix: apical secretion and distribution.

Pigment epithelium-derived factor (PEDF) is an extracellular protein derived from the retinal pigment epithelium (RPE), a tissue formed by polarized cells that release growth and trophic factors in a directional fashion. We have investigated the distribution and directional release of PEDF protein by the monkey RPE. We established primary cultures of monkey RPE cells that expressed the PEDF gene, and that synthesized and secreted the PEDF protein. Northern analysis of RPE cultures and monkey ocular tissues showed that PEDF transcripts were highly expressed in RPE as compared with several other monkey ocular tissues, being even more abundant in cultured cells than they were in the native RPE. The differentiated RPE cells in culture secreted protein that shared the immunological, biochemical and biological characteristics of PEDF. The overall PEDF levels in the RPE conditioned media reached 6.5 mg ml- after 8 days in culture (i.e. 1.1 pg of PEDF per RPE cell). RPE cells were cultivated on permeable supports as monolayers forming a barrier between apical and basal compartments. Apical and basal culture media were sampled at three or four-day intervals for 18 cycles, and the PEDF content was quantified. Most of the PEDF protein was significantly higher in the apical than in the basal medium (>4 times) at the initial recovery intervals, to be detected only in the apical medium at the latter intervals. In the native monkey eye, the concentration of soluble PEDF in the interphotoreceptor matrix (144 nM) was 7-fold and 25-fold greater than in vitreous and aqueous, respectively. PEDF was abundant in the interphotoreceptor matrix surrounding rod and cone outer segments, and was detectable at lower levels in the RPE as visualized by confocal microscopy. We concluded that PEDF synthesized by the RPE is secreted preferentially from the apical surface and is distributed apically to the RPE bordering the outer segments of photoreceptors. PEDF can be a useful marker for RPE polarization and differentiation. The polarization of RPE may be an important mechanism to control PEDF secretion and our results offer interesting possibilities on regulation of PEDF.

Animals↗
PubMed2000

Pigment epithelium-derived factor supports normal development of photoreceptor neurons and opsin expression after retinal pigment epithelium removal.

Dysfunction of the retinal pigment epithelium (RPE), its loss, or separation from the underlying neural retina results in severe photoreceptor degeneration. Pigment epithelium-derived factor (PEDF) is a glycoprotein with reported neuroprotective and differentiation properties that is secreted in abundance by RPE cells. The "pooling" of PEDF within the interphotoreceptor matrix places this molecule in a prime physical location to affect the underlying neural retina. The purpose of this study was to analyze the morphogenetic activity of PEDF in a model of photoreceptor dysmorphogenesis induced by removal of the RPE. Eyes were dissected from embryonic Xenopus laevis, and the RPE was removed before culturing in medium containing PEDF, PEDF plus anti-PEDF antibodies, or medium alone. Control retinas were maintained with an adherent RPE. Light and electron microscopic analysis was used to examine retinal ultrastructure. Opsin was localized immunocytochemically and quantified as an index of outer segment membranous material and photoreceptor protein expression. Removal of the RPE resulted in an aberrant assembly of photoreceptor outer segments, loss of fine subcellular ultrastructure in photoreceptors, and a reduction in opsin protein levels when compared with control retinas. The addition of PEDF prevented the dysmorphic photoreceptor changes induced by RPE removal. In particular, photoreceptor ultrastructure, outer segment membrane assembly, and steady-state levels of opsin were equivalent to control conditions. Anti-PEDF antibodies completely blocked the morphogenetic activity of PEDF. These results indicate that PEDF is able to mimic the supportive role of the RPE on photoreceptors during the final stages of retinal morphogenesis.

Animals↗
PubMed2006

Use of iris pigment epithelium to replace retinal pigment epithelium in age-related macular degeneration: a gene expression analysis.

OBJECTIVE: To determine the gene expression profiles of primary retinal pigment epithelium (RPE) and iris pigment epithelium (IPE) using microarrays. METHODS: Primary RPE and IPE from 6 human donor eyes were collected, and total RNA was isolated. Differences in gene expression were determined using a human genechip (human U95Av2 [12 600 probes]; Affymetrix Inc, Santa Clara, Calif). RESULTS: Hierarchical cluster analysis differentiated the gene expression profiles of RPE and IPE clusters into 2 distinct groups. A mean +/- SD of 5308 +/- 416 gene probes were expressed in RPE vs 6130 +/- 205 in IPE. Sixty-eight genes were expressed only in RPE; 154 genes were expressed only in IPE. Twenty-two additional genes had greater than 3-fold increased expression in RPE vs IPE, and 147 genes had greater than 3-fold decreased expression in RPE vs IPE. CONCLUSION: There are major differences in the gene expression profiles of primary RPE vs IPE. Clinical Relevance The different gene expression profiles of primary RPE vs IPE harvested from the same donor eyes infer that it may be difficult for IPE to replace all aspects of damaged RPE function in transplantation studies.

Aged↗
PubMed1989

Morphology of fungiform papillae in canine lingual epithelium: location of intercellular junctions in the epithelium.

The localization and structure of intercellular junctions and barriers in the extragemmal epithelium of canine fungiform papillae were determined by using both morphological and electrophysiological methods. Gap junctions were located in all epithelial strata with the exception of the stratum corneum, suggesting that the epithelium functions as a syncytium. The extracellular space of the stratum corneum was composed of a discontinuous, three-dimensional network of tight junctions, modified desmosomes, and lamellar bodies. A zonula occludens, which stops the penetration of lanthanum, is present in the uppermost layer of the stratum granulosum. In freeze-fracture replicas, tight junctions appear as extended networks of ridges of variable thickness on the PF fracture face and complementary grooves on the EF fracture face. The relatively high resistance pathway resulting from the layers of corneocytes and networks of tight junctions and lamellar bodies in the stratum corneum is bypassed by the low-resistance pathway provided by the taste pore.

Animals↗
PubMed1994

cDNA from human ocular ciliary epithelium homologous to beta ig-h3 is preferentially expressed as an extracellular protein in the corneal epithelium.

The non-pigmented ciliary epithelium is largely responsible for the formation of aqueous humor in the mammalian eye. To provide a basis for studies at the molecular level, a directional expression cDNA library was constructed in Uni-ZAP XR vector from poly A+ RNA of the human non-pigmented ciliary epithelial derived ODM-2 cell line. Fifty-three cDNA clones were isolated from the library and characterized by partial sequence analysis. Approximately 49% of the clones exhibited homology with known genes in the GenBank/EMBL databases. The putative identification of these clones may reflect the transcriptional activity of the ODM-2 cells in culture. One of the identified clones, ODM-42-I, was found to be specific and highly expressed in the corneal epithelium. This clone had an exact match with a recently discovered human gene, beta ig-h3 (Skonier et al., 1992, DNA Cell Biol., 11:511-522), which codes a surface recognition protein, inducible by transforming growth factor beta (TGF-beta), and containing a putative binding site (RDG) for integrins. The ODM-42-I cDNA clone displays a distinctive pattern of expression found in the human eye, expressed almost exclusively in the cornea. Further studies, using sera from a synthetic peptide to the carboxy-terminal region of ODM-42-I, reveal that the protein is heterogeneous in charge and is preferentially expressed on the extracellular surface of corneal epithelial cells, and might share immunologic properties with integrins beta 1.

Animals↗
PubMed1991

Comparison of glycosidase activities in epidermis, palatal epithelium and buccal epithelium.

1. beta-Glucosidase, alpha-glucosidase, beta-galactosidase and alpha-mannosidase were measured in epidermis, palatal and buccal epithelium of the pig (Sus scrofa). 2. All three epithelia contained similar alpha-mannosidase activity (1.7-3.2 nmol mg tissue-1 hr-1 at pH 4), and none contained significant alpha-glucosidase. 3. Specific activity of beta-glucosidase was high (9-13 nmol mg tissue-1 hr-1 at pH 4) in epidermis and palate, but activity was low (less than 2 nmol mg tissue-1 hr-1) in buccal epithelium. 4. Only epidermis contained a high level of beta-galactosidase (5.8 nmol mg tissue-1 hr-1). 5. Differences in glycosidase profiles may underlie differences in permeability barrier properties in these epithelia.

Animals↗
PubMed1998

Early embryonic interaction of retinal pigment epithelium and mesenchymal tissue induces conversion of pigment epithelium to neural retinal fate in the silver mutation of the Japanese quail.

The neural retina and retinal pigment epithelium (RPE) diverge from the optic vesicle during early embryonic development. They originate from different portions of the optic vesicle, the more distal part developing as the neural retina and the proximal part as RPE. As the distal part appears to make contact with the epidermis and the proximal part faces mesenchymal tissues, these two portions would encounter different environmental signals. In the present study, an attempt has been made to investigate the significance of interactions between the RPE and mesenchymal tissues that derive from neural crest cells, using a unique quail mutant silver (B/B) as the experimental model. The silver mutation is considered to affect neural crest-derived tissues, including the epidermal melanocytes. The homozygotes of the silver mutation have abnormal eyes, with double neural retinal layers, as a result of aberrant differentiation of RPE to form a new neural retina. Retinal pigment epithelium was removed from early embryonic eyes (before the process began) and cultured to see whether it expressed any phenotype characteristic of neural retinal cells. When RPE of the B/B mutant was cultured with surrounding mesenchymal tissue, neural retinal cells were differentiated that expressed markers of amacrine, cone or rod cells. When isolated RPE of the B/B mutant was cultured alone, it acquired pigmentation and did not show any property characteristic of neural retinal cells. The RPE of wild type quail always differentiated to pigment epithelial cells. In the presence of either acidic fibroblast growth factor (aFGF) or basic FGF (bFGF), the RPE of the B/B mutant differentiated to neural retinal cells in the absence of mesenchymal tissue, but the RPE of wild type embryos only did so in the presence of 10-40 times as much aFGF or bFGF These observations indicate that genes responsible for the B/B mutation are expressed in the RPE as well as in those cells that have a role in the differentiation of neural crest cells. They further suggest that development of the neural retina and RPE is regulated by some soluble factor(s) that is derived from or localized in the surrounding embryonic mesenchyme and other ocular tissues, and that FGF may be among possible candidates.

Animals↗
PubMed1990

Generation and characterization of a murine monoclonal antibody to cervical glandular epithelium using mice rendered tolerant to cervical squamous epithelium.

Murine monoclonal antibodies that distinguish glandular from squamous epithelia in human tissue were generated using a procedure that involved tolerization prior to immunization. Tolerization was achieved by injection of newborn (24 hrs old) Balb/c mice with extract of normal cervical tissue containing squamous epithelium (the tolerogen). Three weeks later, mice showing no evidence of antibodies to tolerogen in their sera were immunized with an extract of cervical tissue containing both glandular and squamous epithelia. Following immunization, the sera from mice subjected to this treatment showed strong reactivity with glandular cells but not with squamous cells in sections of frozen tissue examined by an indirect immunohistological method. Spleen cells from mice showing this pattern of serum reactivity were used as fusion partners with a mouse myeloma cell line in order to generate monoclonal antibodies. Following extensive screening, one monoclonal antibody (designated anti-GEA.49) was selected for further study on the basis of reactivity with high affinity to glandular epithelium and a complete absence of staining of squamous and connective-tissue cells. Detailed tests of specificity and patterns of reactivity indicate that the antigen detected by the antibody is expressed on the apical plasma membrane of glandular epithelia and is a glycoprotein with an apparent molecular weight of 49 kilodaltons. Both immunohistological and biochemical methods demonstrated the expression of the antigen on glandular epithelia but not on squamous epithelia from several sources, underlining the usefulness of tolerization/immunization approach for generating antibodies with particular specificity requirements.

Animals↗
PubMed1988

Carcinogen-induced unscheduled DNA synthesis in xenotransplanted human tracheobronchial epithelium: comparison with rat tracheal epithelium.

Extrapolation from rodent genotoxicity data to humans is complicated by variables such as interspecies differences in carcinogen metabolism and DNA repair. A xenograft system containing human bronchial epithelial cells was used to assess the induction of unscheduled DNA synthesis (UDS) by carcinogens and to compare the response with that of rat tracheal epithelium. Cells from human bronchus were grown in explant culture, inoculated into de-epithelialized rat tracheas and implanted subcutaneously into nude mice. Within six weeks, a differentiated mucociliary epithelium lined the xenografted tracheas. Fresh rat tracheas and human xenografts were cut into rings and incubated in media containing [3H]thymidine and either the direct-acting carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG, 3-1000 microM), or a carcinogen requiring metabolic activation, 4-nitroquinoline-1-oxide (4-NQO, 3-100 microM). Tissues were then fixed, sectioned, processed for autoradiography and the number of nuclear grains (NG) determined for 100 epithelial cells lining the trachea in each section. A time- and concentration-dependent increase in NG was observed in both human xenografts and rat tracheas after treatment with MNNG or 4-NQO, indicating induction of UDS by these agents. The UDS response to MNNG in the human xenografts was similar to that observed in the rat tracheas, whereas the response to 4-NQO was greater in rat tracheas. These studies indicate that the human xenograft system should have applications for the study of carcinogen-induced damage in normal bronchial epithelial cells.

4-Nitroquinoline-1-oxide↗