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

In primary monolayer cultures of mature rat hepatocytes, cell growth and hepatocyte-specific functions were mediated by a cell surface component (named the cell surface modulator) via cell-cell contact. The modulator activity was heat-labile and trypsin-sensitive. Activity was also found in plasma membranes from kidney, brain, lung, and erythrocytes. The modulator was solubilized by 4% octylglucoside plus 4M guanidine HCl from liver membranes. The molecular weight of the modulator was 670KD determined by Sephacryl S-400 gel filtration. Hepatoma cells established from Reuber and Morris hepatoma did not show any cell density-dependency on either cell growth or hepatocyte-specific function. However, these hepatoma cells had strong cell surface modulator activity. These results suggest that hepatoma cells have lost their cell density-dependent regulation because they have lost the ability to respond to the cell surface modulator. Characterization of the cell surface modulator and its mechanism of transmitting a signal for gene regulation would be helpful in understanding the process by which cells assemble into tissues in vivo and the mechanism of changes in gene expression in tissue during development, regeneration and carcinogenesis.
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PMID:[Reciprocal regulation of growth and differentiation in hepatocytes by cell surface modulator and loss of regulation during carcinogenesis]. 398 39

The kidney is a key target tissue in animal and human carcinogenesis, yet there are no established short-term tests for studying the genotoxicity of chemicals in the kidney. We have developed an assay for the measurement of chemically induced DNA repair as unscheduled DNA synthesis (UDS) in isolated rat kidney cells following in vivo treatment. Male Fischer-344 rats were injected intraperitoneally with chemicals dissolved in saline or corn oil. After various treatment times, the kidneys were perfused with a collagenase/trypsin solution (CTS), minced into small pieces, and stirred in CTS at 37 degrees C for 1 hr to dissociate cells. Cultures contain a high proportion of epithelial cells from the proximal and distal tubules. Cultures were incubated for 16-18 hr with 3H-thymidine in Williams' Medium E supplemented with 20% fetal bovine serum. UDS was measured by quantitative autoradiography as net grains/nucleus (NG). The percentage of cells in repair (% IR) was defined as the percentage of cells with greater than or equal to 3 NG. Saline- or corn oil-injected controls consistently produced -3 to -5 NG with less than 1% IR. The time course of DNA repair following treatment with the direct-acting mutagen methylmethane sulfonate (MMS) or the renal carcinogen azaserine showed a peak response at 2 hr after treatment. Azaserine showed a rapid decline in UDS at 12 and 24 hr, whereas MMS exhibited a relatively high UDS level at 24 hr. The renal carcinogens methylazoxymethanol acetate, N-methyl-N-nitrosourea, and streptozotocin all yielded strong positive UDS responses. The liver and intestinal carcinogen 1, 1-dimethylhydrazine at doses up to 50 mg/kg was cytotoxic to kidney cells, but induced less than 0 NG. Treatment with 1,2-dimethylhydrazine, which induces kidney tumors in mice but not rats, also induced less than 0 NG. Treatment with o-anisidine, a weak renal carcinogen, did not induce UDS in the kidney, suggesting that it may be acting as a tumor promoter. These results demonstrate the usefulness of this assay for the detection and study of a variety of genotoxic kidney carcinogens.
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PMID:Measurement of unscheduled DNA synthesis in rat kidney cells following in vivo treatment with genotoxic agents. 406 62

Six large hepatic nodules obtained 46 to 74 weeks after a single dose of diethylnitrosamine (0.625 or 1.25 micrograms/gm) in infant C57BLxC3H F1 male mice were studied to elucidate the nature of intracytoplasmic inclusions in the hepatic cells of these nodules. By light microscopy, the nodules constituted a spectrum of lesions ranging from some which were well differentiated adenomas to others which were frank carcinomas. Round or oval eosinophilic intracytoplasmic inclusions were consistently seen in the well differentiated adenomatous lesions. Some of these inclusions were PAS positive and resisted diastase digestion while others were either negative or only weakly PAS positive. By electron microscopy, they were most commonly crystalline, contained a reticulated electron dense material and were located in the distended rough endoplasmic reticulum. On immunofluorescence the inclusions showed marked specific reactivity with antisera against human alpha-1-antitrypsin. The presence of alpha-1-antitrypsin in these inclusions was further supported by the resistance of these inclusions to digestion by trypsin or papain but not by the pepsin or pronase.
Carcinogenesis 1980 Jun
PMID:Alpha-1-antitrypsin in intracellular inclusions of diethylnitrosamine induced hepatomas of C57BLxC3H F1 mice. 626 19

Two epithelial cell lines were established, one from adult C3H mouse and one from adult Fischer rat ventral prostate. These cell lines were obtained from explant cultures, using Ham's F12 medium supplemented with HEPES, insulin, testosterone, hydrocortisone, epidermal growth factor, and 7.5% fetal bovine serum. A low concentration of trypsin and EDTA in Ca++- and Mg++-free phosphate buffer was used for passaging the cells. The rat cell line was established following implantation of prostate tissue in nude mice. These cell lines stained positively for acid phosphatase and were dependent upon epidermal growth factor for growth. Morphological studies, including electron microscopy, revealed a highly characteristic epithelial morphology of both cell lines. These cell lines have hypotetraploid chromosome number and are capable of metabolizing benzo(a)pyrene. We propose the application of these cells as models for the study of prostate carcinogenesis.
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PMID:Development of two cloned epithelial cell lines from normal adult mouse and rat ventral prostates. 627 88

Phorbol ester receptors have been demonstrated in a variety of cells and tissues using [3H]phorbol-12,13-dibutyrate (PDBu) as a ligand. In a search for possible endogenous ligand(s) for the receptor, we used the human placenta as a source. A factor that can inhibit the binding of [3H]PDBu on different types of cells was purified (133-fold) from an extract of human placenta. This factor, PEBIF ('phorbol ester binding inhibitory factor'), is sensitive to pepsin and resistant to trypsin treatment. It is heat- and acid (pH3)-stable and can be precipitated by 80% ethanol with no loss of activity. PEBIF inhibits binding whether it is added before or after incubation of [3H]PDBu with human amniotic membrane cells (FL). Inhibition occurs at both 37 degrees C and 4 degrees C and is rapid and reversible; it does not require intact cells, since it also occurs with membrane fractions. PEBIF does not act like a binding protein for PDBu, and the kinetics of the inhibition on FL cells is non-competitive. Inhibition was also observed in rat liver cells (IAR 6) and Friend erythroleukaemia cells (FELC). Differentiation of FELC induced by hexamethylene bisacetamide can be inhibited by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) only if TPA-sensitive cells (TS 19-101) are used; no inhibition is observed with TPA-resistant cells (TR 19-9). The same is true of PEBIF. It has been shown that these two clones have about the same number of receptors, with no change of affinity; and the extent of inhibition of PDBu binding by PEBIF was similar in the two clones. Like TPA, PEBIF can increase 2-deoxyglucose uptake in mouse fibroblasts (BALB/3T3 cells). These data suggest that this physiological factor may play a role in the regulation of cell differentiation and/or in the modulation of carcinogenesis.
Carcinogenesis 1984 Jan
PMID:Characterization of a human placental factor which inhibits specific binding of phorbol esters to cultured cells. 631 23

Phorbol ester tumor promoters produce a rapid increase in adhesiveness of murine erythroleukemia (MEL) cells. Following treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and other tumor promoters, these cells adhere to the surface of the culture dish or become agglutinated to each other. Structurally related compounds which are devoid of tumor promoting activity failed to induce agglutination of MEL cells. Pentamidine isethionate (PI) and tosylamide-phenylethyl-chloromethyl ketone, two known inhibitors of trypsin-like enzymes, prevent the phorbol esters-induced adherence and agglutination. A short exposure to TPA results in an increase in protease activity at the alkaline pH range. This TPA-induced proteolytic activity is inhibited by PI. Induction of erythroid differentiation by hexamethylene-bisacetamide is associated with a decrease in TPA-induced cell adhesion and TPA-induced proteolytic activity. Taken together, these results suggest the participation of an alkaline proteolytic activity in the membranal changes evoked by phorbol esters.
Carcinogenesis 1983 Nov
PMID:Phorbol ester-induced adhesion of murine erythroleukemia cells: possible involvement of cellular proteases. 635 19

Populations enriched in proliferative, mucous goblet, and absorptive cells were isolated by a method of repeated time dissociation of the colonic mucosa from the adult rat. Five sequential cell suspensions were obtained by rotating the everted colon on 0.2% trypsin solution in Eagle's minimum essential medium at 30 degrees for 20 min each time. Approximately 3.7 x 10(7) cells were obtained from each colon, and 87% of the cells were found viable. The results, based on the [3H]-thymidine-labeling index, [3H]thymidine incorporation, thymidine kinase activity, and histochemical and ultrastructural observations, indicate the Cell Suspension I, separated from the luminal surface, contains 82 +/- 9% (S.D.) absorptive cells; Suspension III, separated from the middle level of the crypts, contains 80 +/- 7% mucous cells. Suspension V, isolated from the crypt base, contains the majority of proliferative epithelial cells (85 +/- 10%). This method provides a suitable tool for a variety of studies in colon carcinogenesis.
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PMID:Isolation and characterization of epithelial cell types from the normal rat colon. 744 57

The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the terminal differentiation of hamster epidermal cells in culture was studied. Epidermal cells were isolated from 1-day-old Syrian hamsters by separating the epidermis from the dermis by cold trypsin treatment. A large number of cells were isolated by this procedure without contamination with dermal fibroblasts. When grown in culture, the epidermal cells divided rapidly, stratified, and differentiated as measured by elaboration of abundant keratin-like amorphous material, red staining with rhodanile blue (which is characteristic of cornifying epithelium), and formation of cornified envelopes. These structures were measured by electron microscopy and quantitation of detergent-insoluble cell ghosts. TPA markedly inhibited this differentiation of the hamster epidermal cells in culture. When grown in the presence of TPA (5 to 1000 ng/ml) for three or more days, the epidermal cell monolayers failed to stain positively with rhodanile blue, and the cell stratification and production of keratin-like material was reduced. The differentiation of the epidermal cells was quantitated by measuring the percentage of cells with cornified envelopes; TPA reduced by up to 70% the number of these terminally differentiated cells. Phorbol didecanoate also inhibited the differentiation of hamster epidermal cells in culture, while phorbol was inactive. The effect of TPA was reversible. When TPA was removed from the media, the cells rapidly differentiated to the same extent as did untreated cells. TPA also stimulated DNA synthesis of the epidermal cells, especially after 10 days in culture when the vast number of cells in control cultures had ceased DNA synthesis. These results are discussed in view of the fact that TPA has not been demonstrated to promote epidermal carcinogenesis in Syrian hamsters.
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PMID:Inhibition of terminal differentiation of hamster epidermal cells in culture by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. 744 6

This study describes several characteristics of a cell line, UHG-RaC '93 derived from rat oral squamous cell carcinoma induced by the carcinogen 4-nitroquinoline-1-oxide (4NQO). The cell line was established from explant cultures without support of fibroblast feeder cells and continued for > 30 passages. UHG-RaC '93 had a high mitotic rate with a population doubling time of 25 h and a high rate of squame production. The first passage had a low colony-forming efficiency in agarose gel, whereas later passages did not grow at all in semi-solid medium. Phenotype selection was furthermore apparent from a gradual increase of the trypsin-detachment time. Cytogenetic analysis showed that UHG-RaC '93 was hypotetraploid with an average of 74 chromosomes. Abnormalities compared to the normal karyotype were assessed and consisted mainly of breakpoints at (1)(q5?3), (3)(p1), (3)(q11q23), (11)(p?11), (13)(p13) and a derivative (12)t(12;13)(q10;q10). The karyotype remained stable for at least 26 passages. The expression of typical epithelioid markers like cytokeratins and desmoglein corresponded with normal rat oral keratinocytes. However expression of alpha 6 beta 4-integrin was altered. Squame production, immunophenotype and anchorage dependency indicated that UHG-RaC '93 had the same features of a well-differentiated carcinoma with a low degree of agressiveness as the original tumour. The stable karyotype of this cell line provides a basis for further analysis of the effect of 4NQO on the genotype, phenotype and behaviour of rat oral keratinocytes.
Carcinogenesis 1995 Nov
PMID:Characterization of a rat oral squamous cell carcinoma cell line UHG-RaC '93 induced by 4-nitroquinoline-1-oxide in vivo. 758 5

To examine the reasons for the high frequency of biliary tract carcinogenesis in individuals with anomalous arrangement of the pancreaticobiliary duct (AAPBD), we investigated the effects on cellular functions of bile acid and trypsin, which are possible risk factors for carcinogenesis found in stagnant bile juice, using a chick embryo fibroblast culture system. Bile acid was found to increase PGE2 synthesis which has been shown to be increased in premalignant lesions, but to suppress the incorporation of [3H]-labelled TdR into DNA. On the other hand, trypsin increased the incorporation of [3H]TdR into DNA, but did not increase PGE2 synthesis. These results suggest that both the bile acid and trypsin present in the stagnant bile juice in AAPBD act to stimulate cell proliferation, but that their mechanisms of action on cell growth differ. Therefore, the combination of these effects of different types of tumor promoters in the stagnant bile juice in AAPBD may account for the high incidence of carcinogenesis.
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PMID:The effects on cellular functions of bile acid and trypsin in stagnant bile juice in anomalous arrangement of the pancreaticobiliary duct. 795 55


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