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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The distribution of intracellular keratin proteins was examined in a variety of urinary bladder lesions of the rat using the immunoperoxidase staining technique. In ethanol-fixed sections, the normal epithelium was strongly positive for keratin staining. Focal regenerative hyperplasia of the bladder epithelium induced by freezing exhibited relatively weak staining. However, diffuse regenerative hyperplasia induced by a single intraperitoneal injection of cyclophosphamide (CP) showed an intensely positive reaction throughout the epithelium. Of the sections fixed with Bouin's solution, the staining reaction was drastically reduced in the normal bladder and the staining was totally negative in the regenerative hyperplasia caused by freezing. Simple hyperplasia induced by a 4-week feeding of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) as 0.2% of the diet exhibited strong reactivity, and nodular and papillarly hyperplasia induced by a 10-week feeding of FANFT was also positive for keratin throughout the lesions. In contrast to the preneoplastic lesions, FANFT-induced transitional cell carcinoma showed differential staining within the tumors. These results suggest that different keratin expression is involved in the proliferative bladder lesions induced mechanically by freezing and chemically by CP or by the carcinogen FANFT.
Carcinogenesis 1985 Mar
PMID:Immunohistochemical study of keratin in proliferative bladder epithelium induced by freezing, cyclophosphamide or N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide in the rat. 257 45

Long-term mouse urothelial cell cultures were routinely established from explants of neonatal mouse bladders. Foci of proliferating cells could be observed one week after the initiation of the explant cultures. These persisted throughout the culture period and up to one year. Expression of keratin proteins confirmed the epithelial nature of the cultured cells. Morphologic analysis of nuclei sorted after DNA flow cytometry revealed a population of DNA-tetraploid and octoploid cells with large nuclei and prominent nucleoli in addition to a DNA-diploid cell population. Both cell populations showed DNA replicative activity as reflected by bromodeoxyuridine incorporation studies and mitotic activity. These long-term primary mouse urothelial cell cultures may prove useful for studies on urothelial cell kinetics and bladder carcinogenesis.
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PMID:Establishment and characterization of long-term primary mouse urothelial cell cultures. 281 28

Gamma-glutamyl transpeptidase (GGT) activity has been demonstrated histochemically in a number of experimentally induced neoplasms and has been suggested as a label for potential precursors for the development of squamous cell carcinomas. This study explores the kinetics of GGT-stained cell populations, their correlation with the hypothesized initiated cells and evidence of malignant transformation of epithelium in hamster buccal pouch by a 15-week regime of tri-weekly topical application of 7, 12-dimethylbenz[a]anthracene (DMBA) in mineral oil. GGT-positive foci were detected histochemically in tissue sections as early as 1 week after application of the carcinogen, when there was no morphological evidence of dysplasia. The average number of the GGT-positive foci in each experimental period was found to increase with time. Even though the majority of the foci were small, consisting of only a single cell or a small group of cells, a few larger GGT-positive lesions were noted, particularly in the later period of the experiment. A total of 66 grossly visible neoplasms were found. Thirty-seven of these were submitted for GGT staining. Thirty-two (86.5%) of these showed patchy GGT activity, primarily in the superficial epithelial cells and/or the keratin. In the non-neoplastic epithelium, the GGT staining could involve any or all layers of cells. GGT activity was not detected in untreated or mineral oil-treated mucosa. The results of this study support the hypothesis that GGT activity may label potential precursors for the development of squamous cell carcinomas.
Carcinogenesis 1987 Jul
PMID:Gamma-glutamyl transpeptidase activity during carcinogenesis of hamster buccal pouch epithelium. 288 1

Specific keratin cDNA probes and monospecific antikeratin antisera were used to analyze mouse epidermis and epidermal tumors for the expression of a type I 47-kDa keratin, K13, normally associated with terminal differentiation of internal stratified epithelia. We demonstrated that this keratin was virtually absent from the entire body epidermis at various stages of development. Also, it was not detected in various forms of acute and chronic epidermal hyperproliferation or in epidermal cells cultured under conditions that favored either cell proliferation or in vitro differentiation. In contrast, K13 was consistently expressed in squamous cell carcinomas of the skin induced by 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate (TPA), whereas papillomas obtained by the same two-stage protocol were distinctly heterogeneous with regard to the expression of this keratin. These findings were true for two different strains of mice (NMRI and Sencar). Papillomas collected from Sencar mice after 12 wk or from NMRI mice after 15 wk of promotion with TPA were either negative for K13 or elicited variable amounts of this keratin. In all cases of positive expression of K13 in tumors, as in normal stratified internal epithelia, both the keratin protein and its mRNA invariably occurred in the differentiating cell compartments. In contrast to what we found in internal stratified epithelia, however, K13 was expressed without its commonly encountered type II 57-kDa partner, K4. Papillomas negative for the K13 protein were also devoid of K13 transcripts. This indicates that the aberrant K13 expression in tumors is regulated at the level of transcription. Our results suggest that K13 may provide a marker for malignant conversion in the mouse two-stage skin carcinogenesis model and may be especially suited for studies of gene expression regulation.
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PMID:Aberrant expression during two-stage mouse skin carcinogenesis of a type I 47-kDa keratin, K13, normally associated with terminal differentiation of internal stratified epithelia. 307 54

Studies examined the binding of radiolabeled 7,12-dimethylbenz[a]anthracene (DMBA) to epithelial DNA of hamster cheek pouch (HCP) maintained in organ explant culture. Adduct formation was studied as functions of [3H]DMBA dose, of the time after single [3H]DMBA applications, and of the route by which the DMBA was administered--either topically or in the culture media. Total DMBA-DNA adduct formation [total binding index (TBI)] was determined by DNA-bound 3H activity, and qualitative binding characteristics were further studied by high-pressure liquid chromatography. [3H]DMBA was applied either in the culture media at concentrations of 0.005-0.5 micrograms/ml or topically in mineral oil or ethanol in doses of 0.005-0.5 micrograms to each tissue fragment. Histopathologic changes in DMBA-treated HCP fragments included substantial aberrations in maturation of cornified and keratin layers and focal squamatization and dysplasia of the basal epithelium--considerable tissue necrosis was encountered in the high-DMBA-dose groups. Dose-response data were qualitatively similar among treatment types, with the greatest TBIs in topical ethanol groups and the lowest TBIs in culture medium groups. Kinetics of adduct formation and removal showed a rapid increase in TBIs to peak values at 24-72 hours followed by a biphasic decrease in TBIs, which leveled off at 7%-20% of peak values at 120-240 hours. Chromatographic analyses of selected samples at various times from all treatment groups showed three major peaks that are likely to be the same 1,2,3,4-tetrahydro-3,4-dihydroxy-1, 2-oxide-deoxyribonucleoside adducts observed in other rodent in vivo and cell culture systems. These results are consistent with those of other laboratories studying DMBA-DNA interactions and suggest that in vitro studies of DMBA-treated HCP explants are useful in studying the molecular nature of DMBA-DNA interactions in oral mucosal carcinogenesis.
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PMID:7,12-Dimethylbenz[a]anthracene adduct formation with Syrian hamster cheek pouch epithelial DNA: in vitro studies in organ explant culture. 313 Apr 86

Carcinogenesis can be operationally and mechanistically divided into at least three major stages--initiation, promotion, and progression. Variations among stocks and strains of mice to susceptibility to multistage skin and liver carcinogenesis appear to be more related to alterations in tumor promotion than tumor initiation; however, the critical events have not been determined. In the mouse skin model the first stage is thought to involve the interaction of a tumor initiator with the genetic material of stem cells leading to an alteration in some aspect of growth control, differentiation, or both. The major effect of tumor promoters, regardless of the type, is the specific expansion of the initiated stem cells in the skin. This appears to occur by both direct and indirect mechanisms that involve the loss of glucocorticoid receptors, differentiation alterations, a direct growth stimulation of the initiated cells, or selective cytotoxicity. The progression stage is characterized by a high level of genetic instability that produces a number of chromosomal alterations. These changes may be responsible for the loss of the high-molecular-weight keratin proteins and filaggrin, increase in gamma-glutamyl-transpeptidase activity, and changes in oncogene expression in squamous cell carcinomas. We have found that a high percentage of squamous cell carcinomas have a trisomy in chromosome 2 that carries both src and abl genes and an increased expression of src and abl. We have also found increased Ha-ras on RNA expression in both papillomas and squamous cell carcinomas. We suggest that the genetic instability of the initiated cells is responsible for most observed changes during skin carcinogenesis.
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PMID:Critical genetic determinants and molecular events in multistage skin carcinogenesis. 332 8

The temporal and spatial regeneration of denuded mouse bladders was characterized using antibody markers to mucosal and submucosal elements in bladder tissue. Mechanical stripping of bladder mucosa resulted in a plane of cleavage in the submucosa leaving the muscle layers intact. Fully regenerated bladders were observed after 14 to 21 days although submucosal elements showed abnormal vacuolation. Implantation of immortalized epithelial cell line BBN3 into denuded bladders resulted in solid tumor formation while, in contrast, transplantation of MB331 showed cystic structures with no indication of invasion. Confirmation of the epithelial and implanted origin of cells lining the lumina of implanted bladders were shown using different keratin antibodies. The benign behavior of MB331 in vivo is suggestive of a cell line representing a preneoplastic stage in carcinogenesis and demonstrates an approach to assess the in vivo phenotype of cell parameters established in vitro.
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PMID:Transplantation of immortalized bladder epithelial cell lines in denuded mouse bladder. 333 61

A culture medium has been formulated to support the long-term proliferation and differentiation of normal murine epidermal cells in primary cultures. This formulation is based upon MCDB-151 modified by the addition of 1.2 mM Ca2+, 1% fetal bovine serum (FBS) or 0.1% purified bovine serum albumin (BSA), trace elements, and growth supplements. For 4-12 weeks, the cultures demonstrate desmosomes, keratin fibers, basal proliferation, and stratification characteristic of keratinocytes. The addition of 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in approximately 70% cellular detachment, but with continued treatment, the remaining cells proliferated to confluence and stratified. This culture medium has application to a number of studies related to skin carcinogenesis in the murine model system that have not previously been possible.
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PMID:A new medium for primary cultures of adult murine epidermal cells: application to experimental carcinogenesis. 382 82

The immunohistochemical distribution of keratin is reported in experimental carcinogenesis in the mouse submandibular gland (SMG). The initial changes included degranulation of granular convoluted tubule (GCT) cells and the appearance of keratin in the degranulated cells. There was a gradual increase in the area showing keratin staining in the altered tubule cells. Duct-like and cystic structures exhibited an intense keratin staining of their lining epithelium. The squamous cell carcinomas induced varying degrees of keratinization and positive immunohistochemical keratin staining. The latter technique provided a useful marker for distinguishing tumor cells of segmental duct origin in the salivary gland.
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PMID:Keratin distribution in precancerous stages of experimental carcinogenesis in mouse submandibular glands. 608 58

A comparative study of the keratin composition of adult and neonatal mouse epidermis, benign and malignant tumors of mouse skin and murine epidermal cells grown in culture revealed striking differences in the keratin polypeptide patterns when analyzed by one-dimensional gel electrophoresis. Not only did the study confirm body-site specific alterations in the keratin patterns within one species, but it also demonstrated that similar to cultured epidermal cells, three malignant skin tumors investigated specifically lacked a group of keratin components with molecular weights larger than 61,000 daltons, which were invariably present in all normal and also in benign tissues. These findings offer the possibility of using keratins as molecular markers of the malignant state of epidermal cells. Two-dimensional gels of the keratin polypeptides of normal epidermis and of benign tumors exhibited spot patterns which could be divided at the 61,000 dalton level into an essentially basic subgroup, comprising the high molecular weight keratins, and an acidic subgroup including the low molecular weight components. The two uppermost proteins of cultured epidermal cells and carcinomas (molecular weights 61,000 and 58,000 daltons) belong to the acidic subgroup in normal tissues as well as in papillomas. However, in the case of malignant tumors and in vitro transformed epidermal cells they showed distinct alterations in charge in that they migrated into the more alkaline part of the gel. The number of spots appearing in the more basic region of the gel could be inversely related to the degree of differentiation exhibited by tumors or in vitro cells.
Carcinogenesis 1980 May
PMID:Keratins as markers of malignancy in mouse epidermal tumors. 616 5


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