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

Isolation of normal human glandular epithelia and their growth and maintenance in vitro have been major problems. The primary objective of studies presented here was to isolate postpubertal, normal human, viable prostatic epithelium for in vitro cultivation. The long-term objective of these investigations was to develop an in vitro human cell model system for studies on prostatic carcinogenesis. A method for isolation of viable, normal and benign human prostatic epithelium, using collagenase for tissue dissociation, is described. Intact acini were isolated, which, on plating gave rise to vigorously growing monolayer cultures of epithelial cells. The purity of epithelial cultures partly depended upon the source of tissue. Specimens of normal prostate and those of benign tissue derived from open prostatectomies provided primarily pure epithelial cultures with occasional fibroblast colonies in some cultures, which could be removed. Cultures from some specimens of transurethral resection of the prostate (TURP) contained many fibroblast colonies due to incomplete separation of acini from the stroma. This resulted from incomplete digestion of denatured tissue caused by electrocauterization during surgery. Cultures established in this manner are being used to study the effects of hormones, vitamins and other growth regulators in order to establish growth requirements of these cells in vitro, which would facilitate their long-term maintenance.
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PMID:Normal and benign human prostatic epithelium in culture. I. Isolation. 9 33

Isolation of preneoplastic cell populations would greatly facilitate analysis of the development of liver carcinogenesis. Suspensions of intact single cells can be prepared in an almost quantitative yield by two-step perfusion of the isolated liver. In the first step the liver is perfused with a Ca2+-free buffer (or with EGTA) in order to irreversibly cleave the desmosomes; in the second step perfusion with Ca2+-activated collagenase dissolves the collagenous extracellular matrix. The resulting single-cell suspension will be a mixture of intact normal and preneoplastic hepatocytes, other liver cell types (mostly Kupffer and endothelial cells), damaged cells, and subcellular debris. Intact hepatocytes can be purified--e.g., by differential centrifugation--but separation of preneoplastic from normal cells has not yet been achieved. Density gradient separation or selection in culture on the basis of the unique properties of preneoplastic hepatocytes (e.g., drug resistance) may prove useful. The use of hepatocyte cultures and liver-derived epithelial cell lines as test systems and models for chemical carcinogenesis in vitro is briefly reviewed.
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PMID:Hepatocyte suspensions and cultures as tools in experimental carcinogenesis. 22 9

The proliferative activity of tumor cells differing in DNA content (ploidy) and nuclearity was investigated in primary hepatocellular carcinomas of the rat by flow cytometric analysis of collagenase-isolated cells immunostained after labelling with bromodeoxyuridine (BrdU) in vivo. The diploid cell fraction in these euploid tumours was higher than in normal liver, and the rate of binucleation as well as the proliferative activity of the binuclear cells was very low. The highest proliferative activity (BrdU labelling index) was found among the diploid tumour cells. The activity in mononuclear tetraploid and octoploid cells was reduced in inverse proportion to their increasing DNA content, possibly suggesting a loss of proliferative potential associated with polyploidization. There was a significant correlation between the proliferative activity of hepatocellular carcinoma cells and nonparenchymal liver cells in the different tumours, indicating that different cell types within a tumour may respond to common growth stimuli. Treatment of tumour-bearing rats with a promoting carcinogen (2-acetylaminofluorene) resulted in significant stimulation of tumour cell proliferation (all ploidy classes), whereas the proliferation of non-parenchymal (stromal) cells in the tumour was slightly inhibited.
Carcinogenesis 1992 Oct
PMID:Reduced proliferative activity of polyploid cells in primary hepatocellular carcinoma. 133 Mar 42

Studies of normal cellular function as well as the understanding of cellular mechanisms of carcinogenesis and other diseases of the large intestine have been limited, particularly due to the lack of long-term culture of normal human large intestinal epithelial cells (NHLIEC). Using the epithelia from surgically resected human colon, we have dissociated a sufficient number of viable NHLIEC and maintained them in in vitro culture for up to 5 months. Normal-appearing human large intestinal mucosal fragments (1 mm2) were treated with 0.01 mg/ml trypsin, 0.2 mg/ml collagenase + 0.1 mM EGTA or 0.1 mg/ml trypsin + 0.1 mM EGTA in a Stomacher laboratory blender to isolate the cells. Compared with other methods, the use of the Stomacher blender combined with low concentrations of proteolytic enzymes yielded greater numbers of cells per gram of tissue, with up to 84% viable cells. Primary and serially passaged NHLIEC were cultured in CMRL-1066, MEM with 5% serum, and serum-free KGM. These media were all supplemented with insulin, hydrocortisone, epithelial growth factor, and bovine pituitary extract. CMRL-1066 was found to be the best medium for NHLIEC. Contaminating fibroblasts were selectively removed by briefly allowing the cells to adhere to the culture vessel and adding 25 U/ml collagenase to the culture media at the first subculture treatment. The epithelial nature and secretory function of the established cells were confirmed by morphological criteria (light microscopy, phase contrast microscopy and electron microscopy), immunoreactivity to cytokeratin, and positive mucin cytochemistry. We propose that using this methodology for the culture and maintenance of NHLIEC for an extended period of time would serve as a valuable model for a variety of investigations.
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PMID:Long-term culture of normal human colonic epithelial cells in vitro. 137 41

The hypothesis that activation of the signal transduction pathways by environmental stress may lead to genetic instability was tested. Mouse T-lymphoma cells, GRSL13, were treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA). The induction of transcription of c-fos, fosB, c-jun, junB and collagenase was studied as well as the mutation rate in the progeny of treated cells. It was found that mRNA levels of fosB, junB and collagenase, all known to be involved in the growth factor signal transduction pathway, were enhanced. No transcription of c-fos and c-jun was observed in control and TPA-treated cells. These results suggest that transcription of c-fos is not a prerequisite for the induction of transcription of collagenase. The degree of induction of the signal transduction pathway was dependent on culture conditions of the treated cells, growing cells having less response than stationary cells. The mutation rate was significantly enhanced in the progeny of TPA-treated cells from 4.2 X 10(-7) to 9.8 X 10(-7)/cell/generation. Fluctuation analysis showed that TPA leads to a temporary enhancement of the mutation rate up to the eighth generation after treatment. The enhancement of the mutation rate is less apparent in growing cells than in stationary cells (1.8- and 2.9-fold respectively) which, because the signal transduction pathways are less induced in growing cells than in stationary cells, is in agreement with the hypothesis that induction of the signal transduction pathway leads to genetic instability.
Carcinogenesis 1991 Mar
PMID:Concomitant induction of signal transduction pathways and genetic instability by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate. 200 94

Both Snell dwarf mice (dw/dw) and their phenotypically normal heterozygotes (dw/+) were dosed with methylclofenapate (MCP) at daily intervals by gavage (25 mg/kg). Animals were killed at 12, 24, 36 and 72 h after the initial dose and the parameters of ploidy, nuclearity and DNA synthesis were measured in hepatocytes isolated by collagenase perfusion. The occurrence of peroxisome proliferation was assessed by electron microscopy after daily administration of 25 mg/kg MCP by gavage for 28 days. The hepatocytes from both phenotypes exhibited similar degrees of peroxisome proliferation but hyperplasia occurred only in the heterozygous animals. The incidence of binulceated hepatocytes in heterozygotes was approximately 50%, and at the end of acute hyperplasia this had reduced to approximately 20%; by contrast the livers of dwarf animals contained approximately 20% binucleated cells and this remained unchanged throughout the period of dosing. The hyperplasia in the wild-type mice, as measured by the occurrence of S-phase, occurred predominantly in binucleated hepatocytes. These observations are further confirmation that acute hyperplasia induced by MCP and similar liver growth inducers occurs predominantly in a sensitive sub-population of binucleated hepatocytes. The results also indicate that peroxisome proliferation and hyperplasia can occur as independent phenomena.
Carcinogenesis 1990 Mar
PMID:Effects produced by the non-genotoxic hepatocarcinogen methylclofenapate in dwarf mice: peroxisome induction uncoupled from DNA synthesis and nuclearity changes. 231 Nov 80

Hepatocarcinoma was induced by administration of diethylnitrosamine to rats. The rats were sacrificed 70 weeks after the administration and the carcinoma nodules were separated from the perinodular parenchymental cells after perfusion of liver with collagenase. The in vitro translational pattern of mRNAs from hepatocellular carcinomas, from perinodular hepatocytes and from regenerating liver after partial hepatectomy were compared by one- and two-dimensional electrophoreses to the pattern obtained with RNA from normal hepatocytes. An increased synthesis of several peptides was observed with RNAs from carcinoma and from regenerating liver and to a lesser extent with RNA from perinodular hepatocytes, which suggests that the increase in synthesis is at least partly related to cell proliferation. A decreased synthesis of several other peptides was observed with RNA from carcinoma nodules and to a lesser extent with RNA from perinodular hepatocytes, but not with RNA from regenerating liver, which suggests that this decrease in synthesis is related to some transformation specific process. These changes are observed as soon as 22 weeks after carcinogen administration. These observations also suggest that at least part of the perinodular hepatocytes have some characteristics of the transformed cells.
Carcinogenesis 1985 Dec
PMID:Changes in poly (A) + RNA translational pattern during chemically induced hepatocarcinogenesis. 241 69

Fumaric acid (FA) suppressed the carcinogenesis in the liver of rats fed 3'-methyl-4-(dimethylamino)azobenzene (3'-Me-DAB), and a study was performed to examine the effect of FA on deoxyribonucleic acid (DNA) synthesis and subcellular structures of hepatocytes under the anticarcinogenic regimens. Male Donryu strain rats were given 3'-Me-DAB by being fed a diet containing 0.06% 3'-Me-DAB for 50 d. They were then given a diet containing 1% FA and drinking water containing 0.025% FA for 53 to 69 weeks. Hepatocytes were isolated from the liver by the collagenase perfusion method and placed in culture, and their activity for DNA synthesis was measured in terms of the incorporation of [3H]dThd into DNA. An enhanced DNA synthesis of hepatocytes was noted in the rats given FA, indicating that FA enhanced the proliferation of hepatocytes to counteract the carcinogenic effect of 3'-Me-DAB. An electron microscopic examination indicated that the distribution of subcellular organella was almost normal in the FA-treated hepatocytes.
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PMID:Inhibitory effect of fumaric acid on 3'-methyl-4-(dimethylamino)azobenzene-induced hepatocarcinogenesis in rats. 251 46

The effect of the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was studied using an immortalized human bronchial epithelial cell line, BEAS-2B, both in vivo and in vitro. The in vivo model consisted of tracheas reconstituted with an epithelium of BEAS-2B cells xenotransplanted into athymic nude mice. Intraluminal TPA treatment caused increased BEAS-2B cell proliferation and downgrowth into the tracheal stroma. In an in vitro invasion assay, TPA enhanced the invasive capacity of BEAS-2B cells 20- to 25-fold. A similar result was observed with diacylglycerol (DAG), an endogenous activator of protein kinase C, and the effects of TPA and DAG were abolished by simultaneous treatment with H-7, a protein kinase C inhibitor. TPA induced type IV collagenolysis, and this effect also was prevented by H-7. These data are consistent with the hypothesis that TPA causes these cells to become invasive by inducing collagenase activity and that this effect is mediated via protein kinase C.
Carcinogenesis 1989 Dec
PMID:Enhancement of the invasive ability of a transformed human bronchial epithelial cell line by 12-O-tetradecanoyl-phorbol-13-acetate and diacylglycerol. 255 20

Techniques are described for the isolation and cultivation of functionally intact mouse hair follicles. Follicles were isolated by collagenase digestion of dermis from 5-day-old mice and purified by differential centrifugation and filtration. Purified follicles were cultured in a Type 1 collagen matrix using Medium 199 and 8% fetal calf serum as the basic nutrient. Viability of follicles was maintained in culture since the cultures incorporated thymidine into DNA and methionine into proteins for at least 7 days. Furthermore, follicles isolated from the collagen matrix after 7 days could reattach to a plastic culture substrate or be further cultivated in a fresh collagen matrix. Functional integrity of cultured follicles was maintained since some follicle-specific cytoskeletal proteins were synthesized in vitro, and follicles isolated from the collagen matrix after 7 days formed a haired skin when recombined with dermal fibroblasts and grafted to a skin site on nude mice. Only a minority of follicles appeared to produce a mature hair shaft in vitro by morphologic criteria, however, and synthesis of the total complement of hair proteins was not observed. Cholera toxin was a strong mitogen for cultured follicles, whereas epidermal growth factor was slightly mitogenic. Epidermal growth factor stimulated the release of a Type 1 collagenase by follicle cells, however. This model system provides an opportunity for the systematic analysis of factors required for the induction of hair growth and the underlying physiology of hair follicle development. This model should also be useful for studying the role of the hair follicle in skin carcinogenesis.
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PMID:Cultivation of murine hair follicles as organoids in a collagen matrix. 282 17


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