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

The carcinogen N-hydroxy-1-naphthylamine reacted with nucleic acids and protein under slightly acidic conditions (pH 5) to form covalently bound derivatives with 3 to 20 naphthyl residues/1000 monomer units. The level of binding was in the following order: DNA greater than polyguanylic acid greater than denatured DNA and ribosomal RNA greater than serum albumin greater than transfer RNA greater than polyadenylic acid. Reactions with nucleosides and nucleotides were not detected, and the binding of N-hydroxy-1-naphthylamine to DNA was not inhibited by the addition of nucleosides, nucleotides, methionine, or glutathione. The reaction rates were first order with respect to both DNA and N-hydroxy-1-naphthylamine concentrations. Enzymatic hydrolysis of the DNA containing naphthyl residues yielded 3 nucleoside-arylamine adducts. The major adduct was identified by chemical, ultraviolet, nuclear magnetic resonance, and mass spectrometric analyses as N-(deoxyguanosin-O6-yl)-1-naphthylamine. The other two adducts were identified as 2-(deoxyguanosin-O6-yl)-1-naphthylamine and its decomposition product. Direct evidence for acid-dependent arylnitrenium ion formation was obtained by isotope exchange upon solvolysis of N-hydroxy-1-naphthylamine in acidic H2 18O, and carbocation formation was indicated by the formation of the solvolysis products, 1-amino-2-naphthol and 1-amino-4-naphthol. These studies demonstrated the conversion of a carcinogenic N-hydroxy arylamine to electrophilic arylnitrenium ion and carbocation species that display high selectivity toward macromolecules. The roles of these electrophiles and their macromolecular adducts in the initiation of urinary bladder carcinogenesis through formation of promutagenic lesions in DNA are suggested.
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PMID:Guanyl O6-arylamination and O6-arylation of DNA by the carcinogen N-hydroxy-1-naphthylamine. 2 2

In tissues of non-lineal rats receiving dimethyl amino-azobenzene (DAAB) or its non-carcinogenic analog diethyl amino-azobenzene (DEAB) there was found, using rabbit serum against an artificial complex RNA + MBSA (methylated bovine serum albumin), the RNA-haptene in the reaction of counter-immunoelectrophoresis in the liver and serum of rats in definite terms since the start of DAAB administration. RSR reaction and immunoelectrophoresis have demonstrated the presence of circulating antibodies against hepatic cell RNA. The kinetic of antibodies against RNA is characterized by their increase after 15 DAAB injections, their decrease to the 60th day and again an increase by the time of the tumor appearance. It is suggested that the phenomena of sensibilization and desensitization to the antigens arising in the process of carcinogenesis play a definite role in "cancelling" the antitumor immunity.
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PMID:[Immunological study of rat liver RNA in the early stages of hepatic carcinogenesis]. 11 37

We have developed and optimized an enzyme-linked immunosorbent assay (ELISA) for absolute quantitation of human beta-glucuronidase. This is a double antibody sandwich system employing two murine monoclonal antibodies specific for human beta-glucuronidase developed in our laboratories. The method involves (a) coating of the high binding polystyrene microtitration plate with the first antibody (7B6 IgG), (b) blocking of remaining active sites with 3% bovine serum albumin in phosphate-buffered saline, (c) application of samples, (d) addition of the biotinylated second antibody (6D2 IgG), (e) addition of streptavidin-horseradish peroxidase, and (f) development of color with o-phenylenediamine dihydrochloride-H2O2 and reading in a microplate reader at a wavelength of 490 nm. The method is highly sensitive with an optimal range of 10 to 100 ng/ml of the enzyme and is reproducible with intraday and interday precisions of 3.2 and 4.1%, respectively. The enzyme contents of 20 urine and 20 bile samples quantitated by this ELISA method were, respectively, 148 +/- 101 and 6380 +/- 3780 ng/ml (means +/- SD) which correlated well with their enzyme activities. Such a method for absolute quantitation of human beta-glucuronidase is essential for studying its pathophysiologic roles in cholelithiasis and carcinogenesis and can also be used clinically as an indicator for tissue damage or malignancy.
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PMID:Development and optimization of an enzyme-linked immunosorbent assay employing two murine monoclonal antibodies for absolute quantitation of human beta-glucuronidase. 141 87

Previous studies have examined Cr(III), or CrO4 reduced to Cr(III), binding in vitro to DNA. However, there have been few studies examining chromate binding to DNA in intact cells. Treatment of intact cells with chromate (Na2(51)CrO4) resulted in chromium (Cr) binding to DNA. The binding of Cr to DNA was much more stable when more residual peptide/amino acids were associated with DNA. A substantial portion of the Cr bound to DNA was released by treatment with EDTA, suggesting that trivalent Cr was the major oxidation state of Cr bound to DNA. Cr(III) stimulated the formation of amino acid-DNA and protein-DNA complexes in vitro. Tyrosine and cysteine exhibited the highest activity in being complexed to DNA by Cr(III) in vitro, while histidine, methionine and threonine also exhibited more activity than any other amino acid. Similar results were found in intact cells. The activity of proteins complexed to DNA by trivalent Cr depended upon the content of these reactive amino acids. Thus, bovine serum albumin was more active than actin, which in turn was more active than histones. These and other studies presented suggested that Cr(III) was involved directly in the formation of DNA-protein complexes in intact cells, unlike other metals such as Ni(II), which are thought to form DNA-protein cross-links catalytically and not participate directly in the complex. The majority of trivalent Cr associated with DNA was bound to the phosphate backbone without exhibiting any base specificity. Collectively, these results indicate that trivalent Cr creates DNA protein crosslinks by binding with reactive amino acids (i.e. cysteine, tyrosine or histidine) and linking these to the phosphate backbone of DNA.
Carcinogenesis 1992 Dec
PMID:Analysis of the binding sites of chromium to DNA and protein in vitro and in intact cells. 147 42

Over the past twenty five years the development of total parenteral nutrition has in many ways revolutionised the practice of surgery. It has enhanced survival in otherwise high mortality operations such as oesophageal surgery, especially with anastomotic complications. It has changed significantly the management of fistulae, either post operative or associated with diseases such as Crohn's enteritis. Here a basic general principle is applied--that a fistula will close if there is no distal obstruction and the throughput can be diminished. This can be achieved by withholding oral feeding and using the parenteral route. It has allowed survival in the short gut syndrome from whatever cause and it is interesting to see the degree of "intestinal adaptation" that occurs once the first critical year is survived with the help of intravenous nutrition. The assessment of nutritional status is difficult and while the level of serum albumin may be taken as a clinical standard, it is obvious that many patients survive extensive surgery with low albumin levels and also that there appears to be a lag period to the restoration of albumin levels, even with otherwise successful nutritional support and with other parameters being satisfactory. Even complex formulae using a combination of laboratory and antropometric parameters is not fully satisfactory as an absolute assessment of nutritional status. It is now interesting to see that nutrition can affect both immune competence and even carcinogenesis. The lipid element in intravenous nutrition may cause dysfunction of immunity and vitamin status, gastric and platelet function with impaired oxygen diffusion leading to increased wedge pressures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intravenous nutritional support and the surgeon: where next? 150 Feb 77

The formation of cross-links between bovine serum albumin and DNA in the presence of chromium(III) chloride was found to be highly pH dependent. In vitro, such lesions were only formed at acidic values of pH, but were not detected at neutral pH. Complexes of chromium(III) and GSH/GSSG similarly failed to induce DNA-protein cross-links at physiological values of pH. Our findings indicate that the cross-links generated in vitro at acidic pH may not be directly relevant to the observed formation of such lesions in cultured cells and that a physiologically relevant in vitro model for the efficient cross-linking of proteins to DNA has yet to be devised.
Carcinogenesis 1992 Feb
PMID:Defining conditions for the efficient in vitro cross-linking of proteins to DNA by chromium(III) compounds. 174 23

Oxidative damage to proteins is known to occur via conversion of side chain amino groups to corresponding carbonyl derivatives. Such damage to enzymes and purified proteins has been quantified previously by reduction with sodium boro[3H]hydride and subsequent measurement of the incorporation of 3H into amino acid fractions. In this study, the NaB3H4 reduction assay was modified to permit the quantitation of free radical-mediated oxidative damage to proteins obtained from animals. Modifications included additional extractions of protein isolates with organic solvents to remove lipids and with nitric acid to remove metal ions. The modified assay has first been validated in vitro by measuring changes in levels of oxidative damage to bovine serum albumin exposed to xanthine plus xanthine oxidase (2-fold increase), to hydrogen peroxide and iron(II) sulfate (5-fold increase), or to gamma radiation (30-fold increase over controls, respectively). gamma radiation of isolated hamster kidney protein also raised the carbonyl content in a dose-dependent manner. The modified assay has then been validated in vivo by measuring the changes in oxidative damage to lung tissue in animals exposed to approximately 85% oxygen (2-fold increase) or to different doses of paraquat (5-fold increase with the high dose over controls, respectively). The assay was then used to examine free radical-mediated oxidation introduced by acute or chronic treatment of hamsters with estrogens, since both synthetic and natural estrogens induce kidney tumors in this species. Priming of hamsters for 3 days with 20 mg/kg/day diethylstilbestrol and treatment with 100 mg/kg of this drug on the 4th day resulted in a 160% increase in free radical modification of renal proteins. Oxidative damage to kidney proteins was also assayed in hamsters treated with estradiol implants for up to 7 months, a regimen known to induce kidney tumors. Significant increases in covalent oxidative modification to renal proteins over values in age-matched controls were detected after 1, 2, and 7 months of continuous estradiol exposure. It is concluded that the modification of the NaB3H4 reduction assay is a useful postlabeling method for monitoring free radical action in vivo. Furthermore, it is postulated that free radical damage in estrogen-treated hamster kidney plays a role in estrogen-induced carcinogenesis.
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PMID:Free radical-induced carbonyl content in protein of estrogen-treated hamsters assayed by sodium boro[3H]hydride reduction. 186 Aug 52

An immunoaffinity column is described that facilitates the analysis of oxidative DNA damage. DNA adducts excised from DNA are excreted in urine and can be assayed as a measure of DNA damage in individuals. Polyclonal antibodies that recognize 8-hydroxy-2'-deoxyguanosine (oh8dG), a biomarker of oxidative damage to DNA, have been produced and their binding properties characterized. The antibodies, raised in rabbits following immunization with protein carrier-hapten conjugates prepared by covalently linking periodate-treated 8-hydroxyguanosine (oh8G) to bovine serum albumin (BSA) or casein, bind oh8dG with high affinity and selectivity, as measured by a competitive radioimmunoassay (RIA). Antibodies obtained from the rabbits immunized with the casein conjugate exhibited a binding affinity for oh8dG of 6.9 x 10(8) M-1. Studies on the relative binding affinities of these polyclonal antibodies for oh8dG, unmodified nucleosides, or derivatives of guanine indicate that the antibodies are suitable for the preparation of immunoaffinity columns that permit us to rapidly isolate oh8dG and 8-hydroxyguanine (oh8Gua) from urine. The high selectivity of the antibodies for oh8dG and oh8G reduces the amount of urinary contaminants previously observed in samples prepared by solid phase extraction, thus greatly facilitating the isolation of these damage products from urine. The relative binding affinity of these antibodies for oh8Gua and 2'-deoxyguanosine were approximately 7.6 x 10(3) and 7.4 x 10(4) fold lower respectively, than the binding affinity for oh8dG. The antibody can be used to quantitate oh8dG in enzymatic hydrolyzates of DNA with values comparable to those obtained by HPLC with electrochemical detection (HPLC-EC).
Carcinogenesis 1991 May
PMID:Immunoaffinity isolation of urinary 8-hydroxy-2'-deoxyguanosine and 8-hydroxyguanine and quantitation of 8-hydroxy-2'-deoxyguanosine in DNA by polyclonal antibodies. 202 51

Aflatoxin B1 (AFB1) exposure from the diet is a major risk factor for the development of liver cancer in people living in regions of China and Africa. Rapid methods to assess the exposure status of these individuals to genotoxic damage imparted by AFB1 will be very important for cancer prevention strategies. Serum albumin is a readily accessible target protein for AFB1 and we report here the development of an accurate and sensitive method to quantitate the major AFB1 serum albumin adduct, aflatoxin-lysine, from less than 100 microliters of serum by combined immunoaffinity chromatography/high-performance liquid chromatography (IAC/HPLC) with fluorescence detection. For this method, serum is digested with Pronase and the adducts are purified by monoclonal antibody IAC and quantified by HPLC. Analysis of human serum samples obtained from an exposed population revealed a highly significant correlation coefficient (up to 0.82 for male samples) between aflatoxin-lysine adduct levels and AFB1 consumption. These data suggest that aflatoxin-lysine is an excellent molecular dosimeter for exposure assessment. To determine whether the liver is the sole site of aflatoxin-albumin adduct formation, preliminary experiments with isolated perfused rat liver were done. These data showed that AFB1 metabolites covalently react not only with albumin in the hepatocyte, but also with circulating proteins in the perfusate. This suggests that a reactive aflatoxin metabolite secreted by the liver may form serum albumin adducts in circulating blood. Taken together, the analysis of aflatoxin-lysine could prove a very useful tool for epidemiological studies.
Carcinogenesis 1990 Nov
PMID:The aflatoxin-lysine adduct quantified by high-performance liquid chromatography from human serum albumin samples. 212 83

An immunoassay now permits the determination of human exposure to aflatoxin at an individual level and consequently allows a better assessment of the role of aflatoxin, and its interaction with hepatitis B virus infection, in the aetiology of liver cancer. Measurements of aflatoxin bound to serum albumin in children and adults from various African countries show that between 12 and 100% contain aflatoxin-albumin adducts, with levels up to 350 pg AFB1-lysine equivalent/mg albumin. In Thailand, lower levels and prevalence of this adduct were observed, while no positive sera were detected from France or Poland. Data are presented showing that exposure to this carcinogen can occur throughout life and the relevance of these observations to the understanding of the multifactorial aetiology of liver cancer in these countries is discussed.
Carcinogenesis 1990 Dec
PMID:Aflatoxin-albumin adducts in human sera from different regions of the world. 226 78


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