Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Green tea, next to water, is the most popular and commonly consumed beverage in the world, especially in eastern countries. In prior studies we have shown that the polyphenolic fraction isolated from green tea (GTP) exerts antigenotoxic effects in various mutagenicity test systems (Mutat. Res., 223: 273-285, 1989) and that its topical application or oral feeding in drinking water protects against polycyclic aromatic hydrocarbon-induced skin tumor initiation and complete carcinogenesis in SENCAR and BALB/c mice [Cancer Lett., 42: 7-12, 1988; Carcinogenesis (Lond.), 10: 411-415, 1989] and UV B radiation-induced photocarcinogenesis in SKH-1 hairless mice [Carcinogenesis (Lond.), 12: 1527-1530, 1991]. In the present study we assessed the effect of skin application of GTP to SENCAR mice on 12-O-tetradecanoylphorbol-13-acetate (TPA) and other skin tumor promoter-caused induction of epidermal ornithine decarboxylase (ODC) activity. Topical application of GTP to mouse skin inhibited TPA-induced epidermal ODC activity in a dose-dependent manner. The inhibitory effect of GTP was also dependent on the time of its application relative to TPA treatment. Maximum inhibitory effect was observed when GTP was applied 30 min prior to topical application of TPA. GTP application to animals also inhibited the induction of epidermal ODC activity caused by several structurally different mouse skin tumor promoters. In order to identify which of the specific epicatechin derivatives present in GTP is responsible for these inhibitory effects, they were isolated from GTP and evaluated for their inhibitory effects against TPA-caused induction of epidermal ODC activity. Among these, (-)epigallocatechin-3-gallate (EGCG), which was the major constituent present in GTP by weight, exerted the maximum inhibition. EGCG also showed greater inhibitory effects against TPA-caused induction of epidermal ODC activity when compared with several other naturally occurring polyphenols. The results of this study suggest that GTP, specifically its epicatechin derivative EGCG, could provide anti-tumor-promoting effects against a wide spectrum of skin tumor promoters.
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PMID:Inhibition of skin tumor promoter-caused induction of epidermal ornithine decarboxylase in SENCAR mice by polyphenolic fraction isolated from green tea and its individual epicatechin derivatives. 161 28

In vitro studies of the effect of aflatoxin B1-dichloride (AFB1-Cl2) on the template function for RNA synthesis of several single- and double-stranded synthetic DNAs containing cytosine and/or hypoxanthine bases are reported. The results indicate: (i) AFB1-Cl2 strongly inhibits the template function of the single-stranded homopolymer polydC and has no effect on polydI, (ii) the inhibition is stronger when cytosine is in the double-stranded alternating copolymer poly[d(I-C)], and (iii) polydI directed RNA synthesis can be inhibited if it is in the double-stranded homopolymer polydI.polydC, although the template function of the polydC strand is still inhibited to a greater extent. The evidence that the selective inhibition of the DNA template function is a direct reflection of the binding specificities of AFB1-Cl2 is provided by the binding studies of [3H]AFB1-Cl2 to these DNAs. The binding of AFB1-Cl2 to polydC is substantiated by the dose-response template inhibition and by the dose-response template binding studies. Additionally, these results show that AFB1 per se has neither inhibitory nor binding activity. Auto radiography of [alpha-32P]GTP labeled RNAs suggests that the mechanism of inhibition of polydC template function by AFB1-Cl2 is mainly due to the inhibition of the elongation of RNA synthesis. Spectrum measurement of the products of enzyme digestion of the AFB1-Cl2 modified polydC reveals that the deoxycytidine fraction gives a typical cytosine absorption peak at 275 nm followed by a broad peak between 300 and 400 nm with a maximum at 390 nm. High performance liquid chromatography confirms the existence of a cytosine-AFB1 adduct which absorbs strongly in the regions between 250 and 400 nm with peaks identifiable at 260, 350 and 390 nm. These results strongly suggest that AFB1 in the activated form of AFB1-Cl2 is able to covalently bind to cytosine in DNA.
Carcinogenesis 1991 Jun
PMID:Evidence for the covalent binding of aflatoxin B1-dichloride to cytosine in DNA. 171 May 45

The effect of aflatoxin B1 (AFB1) on the template function for RNA synthesis of several single and double-stranded synthetic DNAs containing cytosine (C) and/or hypoxanthine (H) bases is studied in vitro. The results indicate that AFB1, after liver microsome activation, strongly inhibits the template function of poly[d(I-C)] and has little, if any, effect on polydI.polydC, polydI, or polydC. This conclusion is reached whether rat liver nuclear free RNA polymerase or E. coli RNA polymerase is used for the transcription. The mechanism of this inhibition is believed mainly due to the inhibition of elongation of RNA synthesis, because autoradiography of the [alpha-32 P]GTP labeled RNAs after polyacrylamide gel electrophoresis clearly shows that the size of the RNA from AFB1 treated group is dramatically reduced. The evidence that the selective inhibition of poly[d(I-C)] template function is a direct reflection of the binding of AFB1 to poly[d(I-C)] is provided by the use of radioactive [3H]AFB1 for the binding and by spectrum analysis of the appearance of a broad AFB1-DNA adduct peak between 300 nm and 400 nm right after the typical DNA peak at 260 nm. These data, which are in direct support to our recent report (F.L. Yu, et al., Carcinogenesis, 11, 475-478, 1990), suggest that the binding of AFB1 prefers alternating, double-stranded DNA, and the binding affinity of AFB1 to DNA is greatly reduced when the bases are in either single- or double-stranded homopolymer forms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transcriptional effect of aflatoxin B1 on cytosine and/or hypoxanthine containing DNAs. 171 92

Hepatocarcinogenesis was initiated in rats with diethylnitrosamine (DEN) followed by a selection with 2-acetylamino-fluorene (2-AAF). Portacaval shunt was then performed in order to promote tumor development. Control rats were not submitted to the initiation--selection protocol and were sham-operated. In control rats, adenylate cyclase activity from crude liver membranes was stimulated 7- to 8-fold by maximal doses of glucagon (10(-6) M) or guanyl-5'-yl-imidophosphate [Gpp(NH)p] (10(-3) M), and 17-fold by a maximal (10(-5) M) dose of forskolin. Guanosine-5'-O-(2-thiodiphosphate) inhibited the response to forskolin (-38%) and to low doses of glucagon (-50%). The initiation--selection protocol increased the activity in basal conditions and in response to various stimuli. The portacaval shunt did not modify the activity of the enzyme with respect to basal activity or the response to glucagon. It significantly decreased the response to Gpp(NH)p (-45%) and to forskolin (-27%). The initiation--selection protocol increased the basal activity of the enzyme (+150%) and its response to Gpp(NH)p (+300%). When tumors developed, the activity of the cyclase further increased (+200%) and an inhibitory effect of GTP on the hormone-stimulated enzyme appeared (-40%). From these results, it is concluded that the promotion of hepatocarcinogenesis by portacaval shunt is coupled with modifications in the activity of adenylate cyclase in response to glucagon and guanylnucleotides.
Carcinogenesis 1992 Feb
PMID:Adenylate cyclase activity in crude liver membranes during chemical hepatocarcinogenesis in portacaval shunted rats. 174 14

Our recent studies have shown that polyphenols present in green tea (GTP) possess significant antigenotoxic activity and afford protection against polycyclic aromatic hydrocarbon-induced skin tumor initiation in mice. In this study we assessed the effect of oral feeding and topical application of GTP on ultraviolet B (UVB) radiation-induced skin carcinogenesis in female SKH-1 hairless mice. Chronic oral feeding of GTP (0.1%, w/v) in drinking water resulted in significantly (P less than 0.01) lower tumor yield (percent of animals with tumors and number of tumors per mouse) and extended TDT50 (P less than 0.05), as compared to animals receiving normal drinking water. Topical application of GTP before UVB irradiation also afforded protection against photocarcinogenesis; however, the protective response was lower than that observed by oral feeding of GTP in drinking water. These results, in conjunction with our prior publications, suggest that consumption of green tea may reduce the risk of some forms of human cancer induced by both physical and chemical environmental carcinogens.
Carcinogenesis 1991 Aug
PMID:Protection against ultraviolet B radiation-induced photocarcinogenesis in hairless mice by green tea polyphenols. 186 Jan 73

gamma-Glutamyl transpeptidase (gamma-GTP) has been noticed as one of the useful markers for malignant transformation of the skin. But the role and mechanism of the induction of gamma-GTP in skin carcinogenesis had not yet been studied. In this report, the authors studied the relationship between gamma-GTP activity and tumor differentiation in squamous cell carcinoma of human skin (SCC). Ten cases of SCC were examined on intensity and localization of the activity of gamma-GTP histochemically by the method of Rutenberg. gamma-GTP activity was found to be more intense in well differentiated SCC than in poorly differentiated SCC. On the other hand, localization pattern of gamma-GTP activity in SCC was not always related to the tumor grade. We concluded that expression of gamma-GTP activity in SCC may reflects the modulating cell differentiation rather than cell proliferation in malignant transformation of the skin. And some of the typical cases were presented.
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PMID:[Expression of gamma-glutamyl transpeptidase related to the tumor differentiation on squamous cell carcinoma of human skin]. 197 39

The induction of ornithine decarboxylase (ODC), a key enzyme of polyamine biosynthesis, is an early and obligatory event in the tumor-promoting step in animal models. The enzyme activity is also elevated in some human premalignant lesions. We determined the ODC activity in human gastric cancer tissue and in the mucosa of cancer-bearing stomach. We concluded that gastric cancer tissue had significantly elevated ODC levels over those of mucosa (157.8 versus 45.7, respectively; P less than 0.05). Among mucosa of the stomach, that of the pyloric gland had higher ODC activity than that of the fundic gland (42.8 versus 21.6, respectively; P less than 0.05). Moreover, mucosa from the cancer-bearing stomach had high ODC activity compared with gastric mucosa without cancer. ODC activity in cancer tissue and mucosa from cancer-bearing stomach was activated by GTP. In rat experiments, the properties of ODC induced by gastric carcinogen were analyzed. Transiently induced ODC by a single gastric intubation of N-methyl-N'-nitro-N-nitrosoguanidine was not activated by GTP whereas constitutively expressed ODC of N-methyl-N'-nitro-N-nitrosoguanidine-induced cancer-bearing stomach was activated by GTP. These results suggest that some tumor-promoting stimuli may be concerned in human gastric carcinogenesis and that mucosal ODC activity may be a useful marker for assessing the risk of gastric malignancy.
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PMID:Increased mucosal ornithine decarboxylase activity in human gastric cancer. 199 84

Crude plasma membranes were prepared from the liver of control rats or of rats submitted to an initiation by diethyl-nitrosamine and selection with 2-acetylaminofluorene and carbon tetrachloride (group IS) or of rats submitted to an initiation-selection protocol followed by a promotion with phenobarbital (group IS PB). In control rats, the diterpene forskolin and glucagon stimulated the activity of adenylate cyclase 6- to 7-fold. Guanosine-5'-O-(2-thiodiphosphate) (GDP beta S) inhibited the stimulation by both agents and the non-hydrolyzable GTP analog, guanyl-5'-yl-imidodiphosphate [Gpp(NH)p], potentiated the stimulatory effect of glucagon. In rats of the IS group, no modification of the activity of the liver cyclase was found, except for an increased response to forskolin and glucagon. In the IS PB group, for the rats without tumor, the only effect of adding phenobarbital was to increase the sensitivity of the cyclase to forskolin. In tumoral tissue, the response to Gpp(NH)p, glucagon and forskolin were increased when compared to the surrounding tissue. In contrast to the surrounding tissue, GDP beta S potentiated the stimulatory effect of forskolin. When the affinity of the glucagon receptors for the hormone was measured in binding experiments, no difference was observed among the rats of the various groups, except for a higher affinity in tumoral tissue. Similarly, GTP inhibited the binding of glucagon with the same potency in each group. It is concluded that during hepatocarcinogenesis, the sensitivity of the adenylate cyclase towards glucagon increases secondarily to a better binding of the hormone to its receptor and to an impairment of the inhibitory regulatory site.
Carcinogenesis 1991 Apr
PMID:Adenylate cyclase activity in crude liver membranes during chemical hepatocarcinogenesis. 201 30

Transfection of the Escherichia coli ada gene coding for O6-alkylguanine-DNA alkyltransferase results in expression of ada in mammalian cells and transmission of nitrosourea resistance to cells lacking alkyltransferase activity. We have used a replication-incompetent retrovirus to transfer into mammalian cells a chimeric gene consisting of 548 bp of the promoter-regulatory region of the gene for P-enolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) linked to ada. The PEPCK promoter was used because it is inducible and highly expressed in liver and kidney cells both in vitro and in vivo. After retrovirus infection of the rat kidney cell line, NRK, intact proviral DNA was integrated into the genome of cloned cells. Individual NRK clones produced up to 200 units/mg protein of bacterial alkyltransferase activity compared to 65 units/mg protein of mammalian alkyltransferase in the parent cell line. Transcription of ada mRNA originating from the PEPCK promoter was induced with Bt2cAMP or dexamethasone and the combination caused a 4-fold increase in ada mRNA while total alkyltransferase activity was induced up to 2-fold. NRK clones expressing ada had up to 2.0-fold increased resistance to 1,3-bis(2- chloroethyl)-1- nitrosourea. Thus, retroviral gene transfer of the PEPCKada chimeric gene allows efficient and inducible expression of ada with a resulting increase in alkyltransferase activity and nitrosourea drug resistance. This retrovirus may be used to study the role of alkyltransferase in repair of mutagenic DNA lesions in mammalian cells in vivo.
Carcinogenesis 1990 May
PMID:Increased drug resistance following retroviral gene transfer of a chimeric P-enolpyruvate carboxykinase (GTP)-bacterial O6-alkylguanine-DNA alkyltransferase gene into NRK cells. 218 1

Effects of ATP and some other nucleotides (AMP, ADP, CTP, GTP, UTP and dATP) on reparative DNA synthesis and repair patch ligation in bleomycin-pretreated permeable mouse sarcoma cells were studied. Reparative DNA synthesis was significantly stimulated by 2.5 mM ATP, ADP or dATP. The stimulation was observed on both DNA polymerase alpha- and beta-dependent reparative DNA synthesis. ATP concentration required for repair patch ligation was much lower than that required for the stimulation of reparative DNA synthesis. An apparent Km value for ATP of the repair patch ligation was about 40 microM. ADP supported repair patch ligation after being converted into ATP by adenylate kinase in permeable cells.
Carcinogenesis 1987 Oct
PMID:Effects of ATP and other nucleotides on DNA repair synthesis in bleomycin-pretreated permeable mouse sarcoma cells. 244 62


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