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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rate constants of 8-oxy-dGMP (8-hydroxy-dGMP) formation upon incubating dGMP in H2O solutions at different temperatures were determined with differential UV-spectroscopy. Extrapolation of rate constant values obtained at elevated temperatures to 37 degrees C gives k = 5.8 x 10(-10) s-1.M-1. The activation energy for the process was estimated to be 24 kcal/mole. In D2O solutions essential lowering of the activation energy (13 kcal/mole) and rising of rate constant (k = 3.7 x 10(-9) s-1.M-1 at 37 degrees C) were observed. The strong influence of D2O on the process points to the possible participation of singlet oxygen in a heat-induced formation of 8-oxy-dGMP. The obtained values of rate constants and activation energy induced by heat show that of all types of DNA damages currently known such as single strand scission, depurination, cytosine deamination and oxidation of guanyl residues to the 8-oxo-derivatives- the last process seems to be the strongest damage of DNA resulting in such biological consequences as mutagenesis, carcinogenesis and aging.
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PMID:[Kinetics of formation of 8-oxy-2'-deoxyguanosine-5'-monophosphate under the effect of heat: determination of rate constants and activation energy]. 133 39

Monoclonal antibodies and rabbit antisera were produced that recognized 4-aminobiphenyl, its major DNA adducts and other metabolites. The antigens used to raise these antibodies were synthesized by coupling the aromatic amine to protein through a diazotization reaction. The goal of this immunization strategy was to induce antibodies that also cross-reacted with most 4-aminobiphenyl-derived metabolites. A total of 20 mice and four rabbits were immunized and every animal produced a strong immune response for 4-aminobiphenyl and its derivatives. Two IgG1 monoclonal antibodies, 3D6 and 2E11, were isolated from two different mouse spleen cell fusions. One of the monoclonal antibodies, 3D6, had a high recognition for the three major 4-aminobiphenyl-DNA adducts: N-(deoxyguanosine-8-yl)-4-aminobiphenyl, N-(deoxyadenosin-8-yl)-4-aminobiphenyl and N-(deoxyguanosine-N2-yl)-4-aminobiphenyl, with affinity constants between 2 and 4 x 10(9) l/mol. In addition, one of the rabbit anti-sera had an affinity constant for the DNA adducts of 2.1 x 10(9) l/mole. Thus, the strategy to use a diazotization coupling reaction was successful at producing high-affinity aminobiphenyl-DNA adduct-specific antibodies. Preparative immunoaffinity resins were made for each monoclonal antibody. These resins quantitatively bound 500 ng each [3H]N-acetyl-aminobiphenyl, [3H]N-aminobiphenyl and [3H]N-(deoxyguanosine-8-yl)-4-aminobiphenyl. Preliminary experiments were performed to test the applicability of the preparative monoclonal antibody immunoaffinity column to isolate [3H]4-aminobiphenyl-derived metabolites in dosed rat and dog urine. About 70% of the radioactivity in rat or dog urine could be bound to the immunoaffinity columns. The combined immunoaffinity column/HPLC analysis of the dog urine led to the identification of a novel urinary metabolite, N-formyl-aminobiphenyl. HPLC analysis of a rat urine sample tentatively found 4-aminobiphenyl, N-acetyl-4-aminobiphenyl and N-formyl-4-aminobiphenyl by co-chromatography, and these compounds accounted for 20, 6.8 and 6.5% of the total radioactivity in the chromatogram respectively. Taken together, these data show that these 4-aminobiphenyl-specific monoclonal antibodies can be used in immunoaffinity columns to isolate metabolites and DNA adducts from biological samples.
Carcinogenesis 1992 Jun
PMID:Monoclonal antibodies and rabbit antisera recognizing 4-aminobiphenyl--DNA adducts and application to immunoaffinity chromatography. 160 Jun 11

Chlorophyllin (CHL), a copper/sodium salt of chlorophyll used in the treatment of geriatric patients, is an anti-mutagen that has been demonstrated to inhibit carcinogen--DNA binding in vivo. To study the mechanism of inhibition, the microsomal metabolism of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and the kinetics of IQ--DNA binding were investigated in the presence and absence of CHL. In time-course studies, CHL produced greater than 80% inhibition of IQ--DNA binding and blocked the metabolism of IQ, such that 80% of the initial dose of carcinogen was recovered unmetabolized from the incubations after 1 h. Kinetic constants were determined for the in vitro DNA binding reaction, with the reaction rate measured as 'pmol IQ bound/mg DNA/min/mg microsomal protein'. Without altering V(max), the Km of the IQ--DNA binding reaction was increased by CHL, and the replot of Km/V(max) versus CHL concentration yielded a straight line with an inhibitor constant of 58.3 microM CHL. Spectrophotometric studies provided evidence in vitro for the formation of a non-covalent complex between CHL and IQ. The CHL--IQ complex had a stoichiometric ratio of 2:1 (mole ratio method) and an apparent dissociation constant from the Benesi-Hilderbrand plot of 1.41 x 10(-4)M at pH 7.4. These results are discussed in the context of a CHL inhibitory mechanism involving enzyme inhibition and molecular complex formation.
Carcinogenesis 1992 Jul
PMID:Inhibition of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA binding by chlorophyllin: studies of enzyme inhibition and molecular complex formation. 163 77

The epidermal melanin unit (EMU) denotes the symbiotic relationship between a melanocyte and a pool of associated keratinocytes. We propose to show that alterations in the biology of the EMU are the main determinant of the different patterns of intraepidermal growth of melanocytes in lentigo maligna melanoma (LMM) and superficial spreading melanoma (SSM). They also appear to affect the biosynthesis of melanin and melanosomes during malignant transformation. Findings in histochemical studies with monoclonal antibodies generated against melanosomal proteins to produce different stains of melanocytes of normal skin, dysplastic melanocytic nevi (DMN), common melanocytic nevi (CMN), LMM, and SSM have led to the suggestion that the altered melanosome synthesis is a main phenotype in the pathophysiology in neoplastic transformation of melanocytes. Altered melanin synthesis may also affect the carcinogenesis in malignant melanoma: pheomelanin is increased in malignant melanoma and DMN, but not in normal skin and CMN. Pheomelanin and its precursors could aid the malignant transformation of melanocytes through the generation of mutagenic ultraviolet photoproducts in familial DMN syndrome.
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PMID:The epidermal melanin unit in the pathophysiology of malignant melanoma. 202 92

Sunlight, particularly its UVB component, is thought to be the most important environmental factor for oncogenesis of melanoma. Its intensity, at the ground level, is a positive function of altitude and a negative function of latitude. Sun exposure and susceptibility in childhood seem to be major risk factors at least in Anglo-saxon countries. UV radiations are able to act as complete carcinogen. Eumelanin/pheomelanin ratio also appears as an important risk factor. Ionizing radiations, heat and traumas have been seldom related to melanoma carcinogenesis. Several chemicals, among them drugs and toxic drugs, add to the list of possible causative agents. Loss of alleles encoding for suppressor factors, caused by UV radiation, might play a significant role in carcinogenesis. A model is proposed, for "mediterranean" vs "caledonian" melanoma, in which the phenotypic sequence melanocytic nevus----melanoma would exhibit peculiar characteristics.
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PMID:[Etiopathogenesis of malignant melanoma of the skin. III. Disease factors inherent in the environment. Pathogenetic hypothesis]. 219 29

In order to evaluate the relative significance of previous grenz-ray treatment for human non melanoma skin carcinogenesis, the files were studied of all patients treated for non melanoma skin cancer of the scalp (n = 82, male/female ratio 1.1) at the Department of Dermatology, the Finsen Institute, from 1976 to 1985. Fourteen patients, with a male/female ratio of 3.7, were treated for squamous cell cancer (SCC). Sixty-five patients, with a male/female ratio of 0.9, were treated for basal cell cancer (BCC). Twelve patients (15%, 11 with BCCs, 1 SCC), of which eight with psoriasis, were previously treated with grenz rays on the scalp, and two of them had not been exposed to additional skin carcinogens. Comparably, malignant conversion in sebaceous and verrucous nevi accounted for 9 cases or 11%. Characteristically, scalp cancers associated with previous grenz-ray treatment were BCCs, the male/female ratio were less than 0.1 and two-thirds occurred in patients with multiple skin cancer. That grenz-ray related scalp cancers more often develop in females than in males was further confirmed by comparison to the sex distribution among patients treated on the scalp with grenz rays in the years 1950, 1960 and 1970 (p less than 0.01). (Accepted August 10, 1988.)
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PMID:Non melanoma skin cancer of the scalp. On the etiology. 256 32

Dose-response relationships for (+/-)-7 alpha,8 beta-dihydroxy-5 beta,6 beta-epoxy-1,4-dimethyl-5,6,7,8-tetrahydrophenanthrene and its 5 alpha,6 alpha-epoxy diastereomer, the syn- and anti-diol epoxides of 1,4-dimethylphenanthrene respectively, have been established for their mutagenicity in Salmonella strains TA98 and TA100 and for their in vivo sister chromatid exchange in the bone-marrow cells of mice. Both isomers were mutagenic in the eta mole per plate range with the syn isomer being in the order of fifteen times more active with TA98 and five times more mutagenic in TA100 than its anti isomer. The anti isomer was more genotoxic in the sister chromatid exchange assay than the syn isomer. Statistically significant results were obtained as low as 1.5 mg/kg body weight for the anti isomer and 3 mg/kg for the syn isomer. The present study supports the inclusion of methyl-substituted bay-region diol epoxides in the concept that the syn isomer, with quasi-diequatorial hydroxyl groups, can contribute to the genotoxicity of the parent polycyclic aromatic hydrocarbons of those compounds which form hindered bay-region diol epoxides.
Carcinogenesis 1989 Jun
PMID:Mutagenicity in Salmonella and sister chromatid exchange in mice for the bay-region syn- and anti-diol epoxides of 1,4-dimethylphenanthrene. 265 64

To study whether fluorescent lighting at work might increase carcinogenesis, hairless mice were exposed to a bank of six 36 W standard fluorescent lamps (neutral-white) every workday for 8 h at an illuminance level of 1,000 lx. For comparison, other mice were exposed to UVB radiation or to simulated solar radiation. In experiment A the animals were irradiated for 6 weeks prior to the application of 7,12-dimethyl-benzanthracene once and--following an interval of 2 days--for 10 weeks after DMBA application. The number of blue nevi and papillomas was enhanced by exposure to all spectra 10 weeks after chemical tumor induction. In experiment B the animals were irradiated for 6 weeks prior to the transplantation of UV-induced fibrosarcoma cells from syngeneic mice into the dorsal and ventral skin. Within the following 4 months fibrosarcoma developed in the dorsal skin exposed to the fluorescent lighting and to the UVB radiation, as well as in the non-irradiated ventral skin of 10-20% of the mice. The results suggest that fluorescent lighting as used in certain work environments may increase carcinogenesis caused by other factors.
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PMID:Fluorescent lighting enhances chemically induced papilloma formation and increases susceptibility to tumor challenge in mice. 309 30

The occurrence of glutathione transferase in human malignant melanoma cell lines and solid tumor material has been analyzed and compared with the enzyme composition in fibroblasts and naevus samples. All cells and tissues investigated contained essentially only the acidic class Pi glutathione transferase as demonstrated by SDS-PAGE and immunoblotting. The enzyme was purified from tumor material and characterized. Its intracellular concentration was significantly higher in all the melanoma cell preparations analyzed than in the non-malignant cells, supporting the view that the class Pi glutathione transferase may contribute to the drug resistance that is characteristic of malignant melanoma.
Carcinogenesis 1987 Dec
PMID:Expression of class Pi glutathione transferase in human malignant melanoma cells. 311 48

The present study describes two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000, which are associated with the transformed phenotype of melanocytes. The monoclonal antibodies (MoAb) MUC18 and MUC54, raised against human malignant melanoma, were selected for differential reactivity with normal and neoplastic cells of melanocyte lineage. The antigen defined by MoAb MUC18 is a membrane bound monomeric sialylated glycoprotein with an apparent molecular weight of 113,000. In contrast to the broad reactivity with melanomas, isolated nevus nests were stained in only 1 of 55 nevi investigated. No staining of MoAb MUC18 was observed in a large variety of surgically removed normal and tumor tissues except for smooth muscle cells of the blood vessel wall and hair follicles. MoAb MUC54 immunoprecipitated a cytoplasmic monomeric protein with an apparent molecular weight of 76,000. By immunoperoxidase staining, the antigen was demonstrated on a large number of melanomas and in addition on 1 of 36 nevocellular, 3 of 4 Spitz, and 5 of 14 dysplastic nevi. The Mr 76,000 protein was found in a number of epithelial tissues and various types of neoplasms. Both antibodies presented in this study define structural changes in the antigenic profile of melanocytes occurring during carcinogenesis.
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PMID:Discrimination between benign and malignant cells of melanocytic lineage by two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000. 354 95


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