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

Tobacco and its related compounds, including snuff, have been implicated in oral cancers. Tobacco-specific nitrosamines have been shown to be the causative agents present in tobacco and its related compounds. Both, N-nitrosonornicotine (NNN) and its butanone derivative (NNK) are carcinogenic in animals. In our in vitro studies using embryonic mouse tongue epithelial cells, NNN is linked to an increase in [3H]dT uptake along with a concomitant increase in ornithine decarboxylase and aryl hydrocarbon hydroxylase activities. NNK, the more potent compared to NNN, causes a further increase in [3H]dT uptake, cell count and ornithine decarboxylase activity. However, aryl hydrocarbon hydroxylase behaves differently in cultures treated with NNK compared to those treated with NNN. Snuff extract has an overall inhibitory effect on cell count, [3H]dT uptake, and ornithine decarboxylase and aryl hydrocarbon hydroxylase activities when administered either alone or in combination with NNN and NNK. How the inhibitory effect of snuff in the presence of tobacco-specific nitrosamines is involved in oral carcinogenesis should be further investigated.
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PMID:Effects of tobacco-specific nitrosamines and snuff extract on cell proliferation and activities of ornithine decarboxylase and aryl hydrocarbon hydroxylase in mouse tongue primary epithelial cell cultures. 260 31

We have compared the regulation of ornithine decarboxylase (ODC) gene expression in primary cultures of hamster embryo fibroblasts and in two independently transformed hamster embryo cell lines. Previous studies have demonstrated that 12-O-tetradecanoylphorbol-13-acetate (TPA) can greatly potentiate the serum growth factor induction of ODC enzyme activity in transformed cells, but not in normal hamster embryo fibroblasts. Treatment of either normal or transformed cells with both TPA and serum yielded greater accumulations of ODC mRNA than with either treatment alone, which is consistent with changes at the protein level. However, treatment of the transformed cells with TPA and serum resulted in a greater increase in steady state levels of ODC mRNA than that observed using normal fibroblasts. The time course for the induction of ODC mRNA was similar for both normal and transformed cells with maximal accumulations 4-8 h after treatment. Studies with actinomycin D further suggests that ODC mRNA is comparatively long-lived in both normal and transformed cells. The accumulation of ODC mRNA after stimulation with TPA and serum is blocked by cycloheximide in normal hamster fibroblasts suggesting that this induction is dependent upon protein synthesis. In contrast, cycloheximide did not affect the accumulation of ODC mRNA under similar treatment conditions in transformed cells. This altered regulation of ODC gene expression in transformed hamster embryo fibroblasts cannot be explained by either gene rearrangement or the amplification of an ODC gene. These data suggest that transformation of hamster embryo cells results in a loss of cellular control over ODC gene regulation which includes an alteration in the requirement for protein synthesis for ODC mRNA accumulation.
Carcinogenesis 1989 Jan
PMID:Regulation of ornithine decarboxylase gene expression in normal and transformed hamster embryo fibroblasts following stimulation by 12-O-tetradecanoylphorbol-13-acetate. 264 50

Because of the importance of human cells, particularly human epithelial cells, in cancer research, we have studied certain phases or events of carcinogenesis using human epidermal cells in primary culture. 1) We found that human epidermal cells are capable of metabolizing benzo[a]pyrene. Large inter-individual variations are found in the basal and induced arylhydrocarbon-hydroxylase activities. 2) UV-induced unscheduled DNA synthesis was demonstrated in human epidermal cells on autoradiographs. We also found that DNA repair is defective in epidermal cells isolated from xeroderma pigmentosum by a new explant-outgrowth culture. 3) Human epidermal cells are unique in that there is a large number of binding sites to phorbol esters compared with mouse epidermal cells, but there is no down-regulation. Further, human epidermal cells show essentially negative responses to tumor promoters, i.e., no stimulation of DNA synthesis, sugar uptake, and no induction of ornithine decarboxylase activity. 4) Human epidermal cells contain 1.5 x 10(5) binding sites per cell for epidermal growth factor (EGF), whereas squamous cell carcinomas of skin and oral cavity have larger amounts of EGF receptors in the order of 10(6) per cell. 5) Based on the above results, we attempted to transform human epidermal cells by the treatment with chemical carcinogens, but until now no transformation was obtained.
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PMID:Use of human epidermal cells in the study of carcinogenesis. 265 1

Methyl-deficient (lipotrope-deficient) diets enhance liver carcinogenesis in rodents. Although the mechanisms responsible for the cancer-promoting activity of such diets have not been identified, they have been observed to cause impaired immune response, alterations in methylation of liver RNA and DNA, and enhanced susceptibility to oxidative damage. Since alterations in gene expression may also play a critical role, the present studies examined the expression of the c-myc, c-H-ras, epidermal growth factor receptor, and ornithine decarboxylase genes, as well as endogenous retrovirus-like sequences, in C57BL/6J x C3H/HeJ F1 mouse liver during the first 2 weeks of feeding of a methyl-deficient diet. The kinetics of liver cell proliferation was investigated in parallel. Increased [3H]thymidine incorporation into liver DNA was found at day 4 and reached a maximum at days 7-11 after commencement of the methyl-deficient diet, when compared to age-matched mice fed a complete diet. Northern blot analysis of polyadenylated liver RNA samples indicated an increase in the levels of RNA homologous to Moloney murine leukemia virus and intracisternal A particle sequences but no significant change in the level of VL30 retrovirus-related RNA in the samples from mice fed methyl-deficient diets. A marked increase in the levels of c-myc and a slight increase in the levels of ornithine decarboxylase and c-H-ras transcripts were seen in the liver RNA samples from the treated mice. Of particular interest was a decrease in the abundance of epidermal growth factor receptor transcripts in the liver RNA samples from the treated mice. These changes in cellular levels of specific RNA resemble, in several respects, those we have previously described in rodent liver during regeneration and tumor promotion and also those seen in rodent hepatomas. They may reflect, therefore, a common profile of gene expression relevant to cell proliferation.
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PMID:Altered expression of retrovirus-like sequences and cellular oncogenes in mice fed methyl-deficient diets. 266 Sep 81

Treating mouse skin with dexamethasone (DXME, 1 mumol) after a single TPA (3.25 nmol) application, inhibited both the dermal inflammatory reaction and the induction of epidermal ornithine decarboxylase (ODC) activity. At the hyperplastic stage, DXME was active against inflammation, though inhibited weakly the induction of ODC. In DXME-protected skin, the hyperplastic stage was delayed; unexpectedly, before that stage, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) induced strongly ODC activity in the epidermal cell layer. Provided that the proliferation process was induced, epidermal cells were increasingly sensitive toward TPA action; they may have been less dependent on inflammatory factors which may modulate the induction of ODC.
Carcinogenesis 1989 Apr
PMID:Epidermal cell proliferation and modulation of the protective potency of dexamethasone against phorbol ester-induced ornithine decarboxylase activity. 270 29

The purpose of this study was to examine the activity and associated kinetic parameters of epidermal protein kinase C (PKC) following stimulation by sn-1,2-dioctanoylglycerol (DIC8) or 12-O-tetradecanoylphorbol-13-acetate (TPA) and to examine the relationship between levels of epidermal PKC activity and the induction of ornithine decarboxylase by these agents, utilizing various stocks and strains of mice. Importantly, the mouse strains and stock used in this study have known differing susceptibilities to undergo TPA-induced tumor promotion: the CD-1 stock and the DBA/2 strain (both sensitive to TPA-induced tumor promotion) and the C57BL/6 strain (resistant to TPA-induced tumor promotion). TPA-stimulated protein kinase C activity was measured in the 10(5)g supernatant fraction of epidermal homogenates using lysine-rich histone as a phosphate acceptor substrate. The maximal velocities for TPA-stimulated epidermal PKC activity in CD-1, DBA/2 and C57BL/6 were 0.28, 0.29 and 0.27 nmol PO4-histone/mg 10(5)g protein/min, respectively. TPA-stimulated epidermal PKC from CD-1, DBA/2 and C57BL/6 had similar theoretical Vmax values and the apparent concentrations of TPA yielding half-maximal stimulation of PKC were also similar. DiC8-stimulated PKC activity to a greater Vmax; however, the concentration required to yield half-maximal stimulation of PKC was one thousand times greater than that of TPA. There were no strain differences in these parameters when the enzyme was stimulated with DiC8. Thus, the levels of epidermal PKC activity in CD-1, DBA/2 and C57BL/6 mice exhibit no strain differences when stimulated by TPA or DiC8 using lysine-rich histone as a phosphate acceptor substrate. Since sn-1,2-diacylglycerols are known effective inducers of epidermal ornithine decarboxylase (ODC) activity, the induction of epidermal ODC was examined in each mouse strain 5 h after topical application of 2 nmol TPA, 5 nmol TPA or 2.5 mumol DiC8. After topical treatment with TPA, C57BL/6 demonstrated an unexpected 2- and 4-fold increase in ODC activity over CD-1 and DBA/2 mice. After treatment with DiC8, C57BL/6 demonstrated a 6- and 10-fold increase in ODC activity over CD-1 and DBA/2, respectively. Thus, the resistant strain (C57BL/6) demonstrated a 'hyperinducibility' of epidermal ODC activity by TPA or DiC8. The time course for the induction of epidermal ODC was examined in each strain, and at every time point measured (3-15 h), the C57BL/6 strain exhibited this 'hyperinducibility' of ODC relative to the other strains. Epidermal DNA synthesis was stimulated to a similar extent in C57BL/6 and CD-1 mice.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinogenesis 1989 May
PMID:Comparison of epidermal protein kinase C activity, ornithine decarboxylase induction and DNA synthesis stimulated by TPA or dioctanoylglycerol in mouse strains with differing susceptibility to TPA-induced tumor promotion. 270 40

Using heterotopically transplanted rat urinary bladder (HTB) system, we previously have shown that contact with urine enhanced bladder carcinogenesis initiated by carcinogen. In order to screen urine for promoter substances, several short term in vitro assays were developed and their results were correlated with the in vivo assay results. Chromatographically separated urine fractions were examined for the inability to induce ornithine decarboxylase (ODC), to enhance incorporation of [3H]thymidine in a bladder carcinoma cell line (804G) and to form colonies in soft agar by NRK-49F. Data from the ODC assay and soft agar colony formation correlated well with the results derived from chronic animal studies. Thus then two assays appear useful in further screening urine for promoter substance. Data furthermore indicate that ODC-inducing urine component(s) may play a primary role in the steps following initiation whereas transferrin, a mitogenic urine component, may play a secondary role.
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PMID:Effects of urinary transferrin and ornithine decarboxylase-inducing fraction on rat bladder carcinogenesis. 271 24

An antitumorigenic effect of sarcophytol A (SaA), a simple monohydroxycembratetraene isolated from a marine soft coral Sarcophyton glaucum, was investigated in rat colon carcinogenesis. Three groups (26 rats each) of female CD-Fischer rats given an intrarectal dose of 2 mg of N-methyl-N-nitrosourea 3 times weekly for Wk 1 to 3 were fed standard laboratory chow in the control group or the chow containing 0.01% SaA from Wk 1 or from Wk 4 in experimental groups. The body weight gain and the food intake were not different among all 3 groups, and SaA intake was similar in both experimental groups at a dosage of 6.18 and 6.14 mg/kg of body weight/day at Wk 5 and 3.87 and 3.90 mg/kg of body weight/day at Wk 25. At autopsy at Wk 26, the incidence of large bowel tumors was found to be significantly lower and the mean number of tumors per tumor-bearing rat to be insignificantly smaller in experimental groups than in the control group: 50% and 58% versus 85%, 1.8 and 1.8 versus 2.0. The tumors in both experimental groups were generally smaller. All the tumors except two signet ring cell carcinomas were well-differentiated adenocarcinomas. Induction of ornithine decarboxylase activity, a marker of tumor promotion, in the large bowel mucosa of rats which were fed the SaA chow for 1 wk, then received an intrarectal dose of 12, 6, or 1.2 mumol of deoxycholate, a tumor promoter in large bowel carcinogenesis, and were killed 4 h later was significantly lower than in control rats. Thus, it was concluded that SaA inhibited the development of large bowel cancer, probably through an antipromoting mechanism.
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PMID:Inhibition of methylnitrosourea-induced large bowel cancer development in rats by sarcophytol A, a product from a marine soft coral Sarcophyton glaucum. 272 Jun 82

Using the heterotopically transplanted rat urinary bladder, we have shown that normal rat urine has a potent tumor-enhancing effect on bladder carcinogenesis. In an attempt to isolate tumor-enhancing factor(s), urine was fractionated by Bio-Gel P-100 column chromatography and each eluate fraction was examined for inducibility of ornithine decarboxylase (ODC) in a target rat bladder carcinoma cell line, 804G. We have identified two ODC-inducible peaks, one located in a high molecular weight region designated as Fraction I (Fr. I) and the second in a low molecular weight region designated as Fraction II (Fr. II). Fr. I consisted of two principal elements, transferrin and a component which induced ODC. The present investigation was conducted to characterize the ODC-inducible activity in Fr. I and II. Chromatographic analysis of Fr. I by Sephacryl S-200 and Fr. II by Bio-Gel P-10 chromatography separated several ODC-inducible peaks. However, the major ODC inducibility was due to a high concentration (460 ng/mg Fr. I residue, approximate Mr 54,000, and 580 ng/mg Fr. II residue, approximate Mr 6,100) of epidermal growth factor (EGF) as determined by radioimmunoassay. Aliquots obtained from these peaks competed with mouse EGF for EGF receptors in A431 cells. Preincubation of Fr. I and II with rabbit anti-rat EGF IgG significantly reduced ODC inducibility. Transforming growth factor alpha activity as determined by radioimmunoassay was also demonstrated in both Fr. I (34 ng/mg) and Fr. II (9 ng/mg). The results of the present study together with our previous data indicate that the majority of the ODC-inducing activity in the tumor-enhancing urinary components Fr. I and Fr. II is due to EGF itself and EGF-related growth factors of high molecular weight and that Fr. I also contains transferrin.
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PMID:Identification of epidermal growth factor as a component of the rat urinary bladder tumor-enhancing urinary fractions. 278 51

Rectal mucosa from normal controls (n = 25) and tumor tissue and rectal mucosa from patients with colorectal cancer (n = 38) and adenoma (n = 35) were biopsied via colonoscopy. Ornithine decarboxylase (ODC) activity was determined in order to study the role of promoters in the process of colorectal carcinogenesis. ODC activity of cancer tissue was significantly higher than that of adenoma tissue. Normal mucosal ODC activity in rectum and sigmoid colon was 2 to 4 times higher than that in the proximal colon. Moreover, rectal mucosal ODC activity was significantly higher in patients with cancer or adenoma than that in normal controls. When ODC activity is regarded as an index of promoter, the possibility is suggested that cancer and adenoma developed in similar mucosa of the large bowel. Furthermore, ODC activity in colon cancer was significantly higher than that in rectal cancer. This suggests the possibility that TPA type promoter assumes a greater role in the process of carcinogenesis of colon cancer than that of rectal cancer.
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PMID:[A study of ornithine decarboxylase activity in tumor tissue and rectal mucosa in patients with colorectal cancer or adenoma]. 279 55


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