Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aflatoxicol, R0, was isolated from Mt. Shasta strain rainbow trout (Salmo gairdneri), and liver homogenates were incubated with aflatoxin B1. Its identity was confirmed by mass, infrared, and ultraviolet spectrometry. The structure was identical to one of the diastereomers prepared by chemical reduction of aflatoxin B1. Aflatoxicol was apparently formed by a reduced nicotinamide adenine dinucleotide phosphate-dependent soluble enzyme of the 105,000 x g supernatant from rainbow trout. Aflatoxicol was not lethal in phosphate buffer to Bacillus subtilis GSY 1057 (metB4, hisA1, uvr-1) nor were aflatoxins B1, Q1, and B2. In the presence of reduced nicotinamide adenine dinucleotide phosphate and trout liver microsomes, aflatoxicol reduced the viability of B. subtilis. Aflatoxin B2, which lacks the vinyl ether present in the other compounds, could not be activated. The product of aflatoxin B1 activation by trout liver microsomes was sought after incubation of 14C-labeled aflatoxin B1. The radioactivity was found in unaltered aflatoxin B1 and in three extremely polar metabolites. The quantity of the new metabolites and the level of microbial lethality was reduced by addition of cytosine and cysteine to the incubation medium. The vinyl ether configuration was a structural requirement for activation, and this finding and the nature of the enzymatic reaction were consistent with the hypothesis that the compounds were metabolized to highly reactive and unstable electrophilic products which bound to nucleophiles such as cytosine and were lethal to B. subtilis. The formation of aflatoxicol as the major product of trout liver metabolism is of great significance considering that it could be activated to a lethal compound and that rainbow trout are one of the most sensitive species to aflatoxin B1-induced carcinoma.
Cancer Res 1976 Jun
PMID:Aflatoxin B1 metabolism to aflatoxicol and derivatives lethal to Bacillus subtilis GSY 1057 by rainbow trout (Salmo gairdneri) liver. 0 90

Cysteine had been reported to increase survival time in thymoma-bearing mice and the interpretation suggested was that this was due to inhibition of a collagenase activity associated with some tumor cells by a chelating action of cysteine. In the present work it was shown that cysteine was a particularly potent inhibitor of amino acid transport into S37 ascites tumor cells, raising another possible interpretation of the earlier data. Sarcomas have previously been reported to lack collagenase activity; a survival study using S37 cells was therefore undertaken in an attempt to distinguish between possible interpretations of the earlier data involving thymomas. A null result was obtained with either cysteine or EDTA, reinforcing the earlier interpretation that survival enhancement with thymoma-bearing mice was due to an effect on collagenase. Other sulfhydryl analogs were found to inhibit transport also, and the effect was more pronounced with system L than system A. The reason for cysteine's particularly potent action on amino acid transport may be associated either with chelation of a metal ion involved in transport, or the involvement of the gamma-glutamyl cycle in the support of amino acid transport.
Cancer Biochem Biophys 1977
PMID:Effects of cysteine upon tumor cells. 2 29

Control rats or rats bearing Morris hepatoma 5123C (intact), 5123C (adrenalectomized), 7794A, 7800, 8999, 9121, or 9618A were fed a purified diet either deficient or adequate for vitamin B6. The concentration of pyridoxal phosphate in the plasma, host livers, and hepatomas was determined, as well as the in vitro rate of inactivation of induced tyrosine aminotransferase in homogenates of host livers and hepatomas. The results demonstrated the presence of a cysteine-independent inactivating system for tyrosine aminotransferase in hepatomas 5123C (adrenalectomized), 7800, 8999, and 9121. Only in hepatoma 9121 was there a dramatic influence of the dietary vitamin B6 on the rate of cysteine-independent inactivation. A cysteine-dependent inactivating system for the enzyme was present in all host livers and hepatomas. The rate of this in vitro inactivation for both host livers and hepatomas apparently was a function of the concentration of pyridoxal phosphate, but inactivation of tyrosine aminotransferase occurred at a significantly lower concentration of pyridoxal phosphate in the hepatomas than in the host livers.
Cancer Res 1979 Aug
PMID:Effects of dietary vitamin B6 on the in vitro inactivation of rat tyrosine aminotransferase in host liver and Morris hepatomas. 3 80

A specific collagenase (EC 3.4.24.3) has been found and purified from serum-free culture medium of 11095 epidermoid carcinoma of rat prostate. The molecular weight of this collagenase was estimated at 71 000 and the pH optimum was approx. 7. At 26 degrees C, the collagenase cleaved collagen at a site 3/4 the length from the N-terminus. At 37 degrees C, this collagenase degraded collagen to smaller peptides. The enzyme activity was inhibited by serum, cysteine and EDTA, but not by protease inhibitors. The presence of collagenase in rat tumor tissue suggests that this enzyme might play a significant role in tissue invasion by cancer cells.
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PMID:Collagenase activity in cultures of rat prostate carcinoma. 3 9

Plasma and prostatic fluid from man, dog, and baboon were measured for carcinoembryonic antigen (CEA) by a radioimmunoassay technique. No CEA was detected in plasma, prostatic fluid, or seminal fluid in 12 dogs and three baboons. Elevated CEA (less than 2.5 ng/ml) was found in 13 of 20 human prostatic fluids. It was inferred that there was no immunologic cross-reactivity of CEA among man, dog, and baboon. CEA has been isolated and purified from liver tumors. Biochemical studies reveal that CEA consists of 60 percent carbohydrate and 40 percent protein. It contains the following carbohydrates: fucose, mannose, galactose, sialic acid, N-acetylglucosamine, and a small amount of N-acetylgalactosamine. The following amino acids were found in CEA: lysine, histidine, arginine, aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, emthionine, isoleucine, leucine, tyrosine, phenylalanine, and cysteine. The amino acid sequence (first 30 amino acids) of the N-terminal has been determined. The N-terminal amino acid was lysine. Using this study as a model, other tumor antigens from prostatic tumor tissues are being investigated. The acid phosphatase isoenzyme from prostatic tissue was also studied. After a series of purifications, two chromatographic fractions were obtained. Treatment with neuraminidase removed the sialic acid content of the molecule, changed the isoelectric focusing patterns, and abolished the chromatographic heterogeneity. Sedimentation studies indicated a molecular weight of about 100,000. Biochemical studies showed that prostatic acid phosphatase isoenzyme is a glycoprotein which consists of 7 percent carbohydrate and 93 percent protein. It contains fucose, galactose, mannose, sialic acid, N-acetylglucosamine, and the following amino acids: aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine, methionine, isoleucine, leucine, tyrosine, phenylalanine, lysine, histidine, arginine, tryptophan, and cysteine. An antiserum to this purified prostatic acid phosphatase isoenzyme is being prepared in animals.
Cancer Chemother Rep
PMID:Tumor antigen and acid phosphatase isoenzyme in prostatic cancer. 4 19

Carcinoembryonic antigen (CEA) has been shown to contain no free cysteine thiol groups but 6 cystine disulphide bonds. 5'5-Dithiobis-(2-nitrobenzoic acid) (DTNB) will react with CEA only after reduction of the disulphide bonds with dithioerythritol. Reduction-alkylation of CEA using dithioerythritol and bromo-[1-14C] acetic acid confirmed the presence of 6 disulphide bonds, as did oxidation of the glycoprotein with performic acid. The products from the DTNB and reduction-alkylation treatments of CEA had less capacity to inhibit the binding of [125I]-CEA to anti-CEA in a radioimmunoassay than the original CEA but could, in sufficient quantities, totally inhibit the binding. Removal, using mercaptoethanol, of the thiol blocking groups from the DTNB-treated CEA resulted in a 55% recovery of antigenic activity. The product from the performic acid oxidation could only inhibit approximately 50% of the binding. Treatment of CEA with 0.533M sodium periodate (NaIO4) greatly reduced its antigenic activity, presumably a result of the oxidative cleavage of the disulphide bonds. No loss in activity, however, was observed when 5.33mM NaIO4 was used, and one Smith degradation (i.e. treatment in sequence with periodate, borohydride and mild acid) of CEA removed approximately 50% of the carbohydrate, including all of the fucose, sialic acid and 2-acetamido-2-deoxygalactose but did not change the antigenic activity.
Br J Cancer 1975 Dec
PMID:Studies on the structure and immunological activity of carcinoembryonic antigen - the role of disulphide bonds. 5 86

Prepared with nonimmunospecific proteins were covalent conjugates of triaziquone [2,3,4-tris(1-aziridinyl)-p-benzoquinone] (hereafter referred to by the tradename, Trenimon). The bound Trenimon that absorbs maximally at 350 nm (epsilon = 8,200) was assayed by titration of the acid uptake during alkylation of thiosulfate ion and by the color produced during alkylation of 4-(p-nitrobenzyl)pyridine. Conjugates of Trenimon with nonimmune IgG were toxic to cells in culture, although no firm binding of conjugate to cell surface could be measured by fluorescein labeling. Inhibition of cellular pinocytotic activity with cytochalasin B had no effect on the cytotoxic response. Polyoma virus-transformed baby hamster kidney (BHK) cells that were threefold more resistant to the action of a conjugate than was the parent cell line were as sensitive as normal BHK cells when grown in the presence of dibutyryl cyclic AMP or when acted on in suspension by the conjugate. These conditions did not affect the response of the parent BHK line. Cysteine acted to protect both cell lines. The results suggest that Trenimon bound to nonimmmune protein reacted primarily with a component of the cell surface. The reaction did not appear to depend on a firm attachment of the conjugate to the cell.
J Natl Cancer Inst 1978 Feb
PMID:Comparisons of the chemical and biologic properties of triaziquone and triaziquone-protein conjugates. 7 16

Supercoiled DNA duplexes of phages phiX 174 and PM2 were treated in aqueous solution at neutral pH with ultimate and proximate carcinogens. Subsequently, the carcinogen-treated phage DNAs were subjected to velocity sedimentation in neutral and alkaline sucrose to quantitative introduction of single strand breaks. Reaction of phage DNA with the ultimate carcinogens N-methyl-N-nitrosourea (MeNOUr), N-ethyl-N-nitrosourea (EtNOUr), 7-bromomethyl-benza[a]-anthracene, N-acetoxy-2-acetylaminofluorene [(Ac)2ONFln] and K-region oxides for short periods followed by sedimentation in neutral sucrose gradients led to very few breaks. Incubation with the proximate carcinogens N-hydroxy-2-acetylaminofluorene, 2-acetylaminofluorene, 7-methyl-, and 7,12-dimethyl-benza[a]anthracene did not result in breaks. However, when the phage DNAs were reacted with the ultimate carcinogens under the same conditions but subsequently alkali-denatured and sedimented in alkaline sucrose gradients, single strand breaks were readily introduced. Incubation with the proximate carcinogens followed by alkali denaturation and sedimentation in alkaline sucrose showed that only 7,12-dimethyl-benz[a]anthracene and, to a minor extent, 7-methyl-benz[]anthracene caused alkali-inducible breaks. The ability of N-methyl-N'-nitro-N-nitrosoguanidine to effect breakdown of superhelical phage DNA in alkali was found enhanced in the presence of N-acetyl-cysteine.
Z Krebsforsch Klin Onkol Cancer Res Clin Oncol 1977 Oct
PMID:Detection of strand breaks in phiX 174 RFI and PM2 DNA reacted with ultimate and proximate carcinogens. 14 49

RNA sulfurtransferase activity has been detected in rat liver and in hepatomas from rats fed a diet containing 0.06% 3'-methyl-4-dimethylaminoazobenzene for 14 to 18 weeks. The reaction measured was the transfer of sulfur from cysteine to acceptor sites in Escherichia coli B transfer RNA (tRNA). Specific activities of the enzymes in liver and hepatoma supernatant fractions were similar, as were the rates and extents of sulfur transfer to tRNA. DEAE-cellulose chromatography of digests of the [35S]tRNA reaction products revealed 3 peaks associated with nucleotide material, the amounts of these peaks differing in tRNA from liver and hepatoma systems. This may suggest differences in specific sulfurtransferases in these tissues.
Cancer Res 1975 Dec
PMID:RNA sulfurtransferase activity in rat liver and chemically induced hepatomas. 17 28

1. Titration of Neurospora tyrosinase with 2-mercaptoethanol shows that the increase of absorbance at 700 nm is directly correlated to the loss of enzymatic activity. Approximately 2 mol of 2-mercaptoethanol per mole of protein are needed for full development of the green, enzymatically inactive complex. The increase of absorbance at 700 nm is also proportional to the intensity of the EPR signal and the amount of non-covalently bound 2-[35S] mercaptoethanol to the enzyme. The maximal EPR intensity reaches 70% of the protein concentration and at most 0.7--0.8 mol of 2-[35S] mercaptoethanol is bound per mol of enzyme. 2. Stopped-flow measurements show that in the reaction between 2-mercaptoethanol and Neurospora tyrosinase a raction intermediate with a strong absorption band at 360 nm is formed in an apparent second-order reaction. This intermediate displays no EPR-detectable signals. The intermediate decays in a similar complex fashion as the absorption band at 700 nm is formed. 3. The reaction of Neurospora tyrosinase with a variety of sulfhydryl compounds was also investigated. In most cases green coloured, enzymatically inactive complexes are formed displaying slightly different EPR signals. However, with cysteine and cysteamine violet coloured, enzymatically inactive complexes are formed which show rather different EPR signals. The integrated EPR intensities amount to 40--70% of the protein concentration. Based on simulations of 9 and 35 GHz spectra all observed EPR spectra can be represented as true S = 1/2 systems. The cysteamine complex can be interpreted as arising from a mixed valence Cu2+ . Cu+ complex. The 2-mercaptoethanol spectra can, however, arise from sulphur radicals. 4. Treatment of Agaricus bispora tyrosinase and Cancer pagures hemocyanin with 2-mercaptoethanol results in green-coloured, EPR detectable complexes similar to the one found with Neurospora tyrosinase. No such complexes are formed when hemocyanins from Helix pomatia and Panulirus interruptus were treated with this reagent.
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PMID:The reaction of mercaptans with tyrosinases and hemocyanins. 20 26


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