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

The effect of metal activators on the fidelity of DNA synthesis has been examined. Using the DNA polymerase from avian myeloblastosis virus, the accuracy of Co2+-, M2+-, and Ni2+-activated DNA synthesis was determined with different polynucleotide templates. With poly[d(A-T)] as the template, the error frequency for dCMP incorporation was 1:1400, 1:1100, and 1:600 for Mg2+, Co2+, and Mn2+, respectively, at maximally activating concentrations. The error frequency was invariant with respect to [Mg2+] but increased with greater than activating concentrations of Co2+ and Mn2+. This increase resulted from differential rates of complementary and noncomplementary nucleotide incorporation. The enhanced error frequency was nonspecific as it occurred with all polynucleotide templates and with all noncomplementary deoxy- and ribonucleotides which were tested. Nearest neighbor analyses of the reaction products indicated that the noncomplementary deoxynucleotides were incorporated as single base substitutions. The fidelity of Ni2+-activated DNA synthesis was invariant with respect to [Ni2+] and was similar to that obtained using Mg2+. During DNA synthesis with Mg2+, the addition of Co2+, Mn2+, or Ni2+ resulted in a decrease in the fidelity of DNA synthesis. The relationship between decreases in the fidelity of DNA synthesis and metal mutagenesis, or carcinogenesis, or both, is considered.
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PMID:On the fidelity of DNA replication. Effect of metal activators during synthesis with avian myeloblastosis virus DNA polymerase. 86 97

Protein tyrosine kinase (PTK) activities in methyl nitrosourea (MNU)-induced rat mammary carcinoma has been investigated by using poly (glu: tyr; 4:1) as an exogenous substrate. The PTK activity of the mammary carcinoma was almost equally distributed between the particulate and soluble (cytosolic) fractions at 110,000 X g. The activity of the particulate enzyme was stimulated by non-ionic detergent Triton X-100 by about 2-fold whereas the detergent had no effect on the cytosolic form. More than 60% of the particulate enzyme could be solubilized by 5% Triton X-100. Although, both particulate and cytosolic PTKs catalyzed the phosphorylation of several tyrosine containing synthetic substrates to various degrees, poly (glu: tyr; 4:1) was the best substrate (apparent Km. 0.7 mg/ml). Both forms of enzymes utilized ATP as the phosphoryl group donor, with an apparent Km of 40 microM. Among various divalent cations tested, Co2+, Mn2+ and Mg2+ were able to fulfill the divalent cation requirement of both forms of the PTKs. All these cations exerted biphasic effects on the kinase activities, however, Mg2+ was the most potent cation. Agents such as epidermal growth factor, insulin and platelet derived growth factor which stimulate their respective receptor-PTK activities were without effect on PTK activities of mammary carcinoma. On the other hand, though heparin and quercetin inhibited both enzyme activities in a concentration dependent manner, the particulate form was more sensitive to inhibition than the cytosolic form. These data indicate that MNU-induced rat mammary carcinoma expresses both particulate and cytosolic forms of PTKs and that there are significant differences in the properties of the two forms of PTKs. Differential effects of some agents on mammary carcinoma PTKs suggest that these enzymes may be acutely regulated in vivo and could play an important role in mammary carcinogenesis.
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PMID:Biochemical characteristics of cytosolic and particulate forms of protein tyrosine kinases from N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinoma. 192 15

Cancer incidence in 433 McKee-Farrar total hip replacement patients, operated on between 1967 and 1973, was examined for 5729 person-years, to the end of 1981. The expected number of natural deaths was slightly higher than observed, suggesting some selection of the operated patients. The risk of total cancer incidence did not increase, but the risk for site-specific cancer did because there were no cases of kidney or bladder cancer, or rare forms of cancer. The risk of leukemias and lymphomas increased, and the risk of breast cancer decreased; these results were surprisingly similar to those of a study from New Zealand. This study concluded that patients with total hip prostheses have a cancer morbidity differing from the general population. The role of chrome-cobalt-molybdenum alloy in carcinogenesis requires further investigation.
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PMID:Cancer risk after Mckee-Farrar total hip replacement. 200 81

Cells from an established line of normal rat hepatocytes (IAR 20) were irradiated with 3 Gy gamma-radiation from a cobalt source to generate transformed clones. Cells from four transformed colonies were compared with the parent cell line by flow cytometry following staining with ortho-phthalaldehyde and propidium iodide to quantitate protein thiols and DNA respectively. Transformed cells exhibited an increased variability in cellular protein thiols which was most evident in G1 and S phase. The altered pattern of macromolecular thiol distribution implies early changes in redox state and/or modification of the amounts or types of sulphur-containing proteins in transformed cells.
Carcinogenesis 1990 Aug
PMID:In vitro transformation induces abnormal protein thiol levels in rat liver cells. 238 31

Case reports of malignant tumors at sites of metal orthopedic implants in humans and domestic animals reviewed; results of carcinogenesis bioassays of implanted metal alloys and of nickel, chromium, cobalt, and titanium powders in rodents are summarized; mobilization of metals from implanted prostheses is discussed; and in vitro assays for morphological transformation of mammalian cells by metal compounds are surveyed. These considerations suggest that occurrence of sarcoma at the implantation site constitutes a complication, albeit rare, of implanted orthopedic prostheses. The author recommends (a) that orthopedic surgeons select prostheses with minimal susceptibility to metal corrosion and wear and, if feasible, replace implanted prostheses when there is evidence of corrosion or mechanical failure; (b) that epidemiological studies be undertaken to quantify cancer risks in patients with various types of metal implants; (c) that an international registry of implant-associated tumors be established; and (d) that research be focused on improved in vitro assays for carcinogenicity of alloys intended for use in orthopedic prostheses.
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PMID:Carcinogenicity of metal alloys in orthopedic prostheses: clinical and experimental studies. 267 72

This study was designed to explore further the hypothesis that the special resistance phenotype seen in hepatocyte nodules during liver carcinogenesis could have a physiologic correlate in the manner with which a carcinogenic xenobiotic is handled. Hepatocyte nodules were induced in male rats by continuous or intermittent exposure to dietary 2-acetylaminofluorene over a 25-week period. Two or 5 weeks after the exposure, the animals were given a single dose of 9-14C-2-acetylaminofluorene. The amounts and rates of excretion of unconjugated compound and derivatives and of the glucuronic acid metabolites in the bile and urine and the amounts in the blood and liver were measured over a period of 180 minutes. For comparison, animals fed the basal diet alone, animals injected with phenobarbital or 3-methylcholanthrene, animals receiving a single dose of cobalt heme and animals fed the 2-acetylaminofluorene for only 2 weeks were studied. These groups were used as controls for different patterns of drug metabolism, especially relating to the cytochromes P-450. The nodule-bearing animals showed a pattern of handling of the carcinogen that is quite different than that of the animals of any other group. They excreted in the bile plus urine from 20 to 30% less. However, relatively much more was in the urine. The free and glucuronide-conjugated metabolic products of the carcinogen were assessed by high performance liquid chromatography. The nodule-bearing animals and the animals treated with 3-methylcholanthrene excreted much more glucuronic acid esters. The pattern of distribution of labeled 2-acetylaminofluorene is different in the nodule-bearing rats than in other animals in which variations in phase I and phase II drug-metabolizing enzymes were induced by treatment with cobalt heme, phenobarbital, 3-methylcholanthrene or short-term exposure to dietary 2-acetylaminofluorene.
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PMID:Kinetics of excretion of 2-acetylaminofluorene in normal and xenobiotic-treated rats and in rats with hepatocyte nodules. 292 79

Radiation induced DNA double strand breaks are believed to be important lesions involved in processes related to cell killing, induction of chromosome aberrations and carcinogenesis. This paper reports the effects of the radioprotector 2-[(aminopropyl)amino]ethanethiol (WR-1065) on radiation-induced DNA damage and repair in V79 cells using the neutral elution method performed at pH 7.2 or pH 9.6. WR-1065 (4 mM) was added to the culture medium either 30 minutes prior to and during irradiation with Cobalt-60 gamma rays (for dose response experiments) or during the repair times tested (for DNA rejoining experiments). The results indicate that WR-1065 is an effective protector against the formation of radiation-induced double-strand breaks in DNA as measured using a neutral elution technique at either pH. The protector reduced the strand scission factors by 1.44 and 1.77 in experiments run at pH 9.6 and pH 7.2, respectively. The kinetics of DNA double-strand rejoining were dependent upon the pH at which the neutral elution procedure was performed. Unlike the results obtained with alkaline elution, rejoining of DNA breaks was unaffected by the presence of WR-1065 at either pH.
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PMID:The effect of 2-[(aminopropyl)amino] ethanethiol (WR-1065) on radiation induced DNA double strand damage and repair in V79 cells. 360 41

Some metals are essential oligo-elements for man. However, if the body load of these same metal derivatives becomes excessive they may be responsible for deleterious effects, particularly cytotoxic ones. Metals are divided into four categories: potent carcinogens; presumptive carcinogens with a documented cocarcinogenic effect; ascertained cocarcinogens; metals with no demonstrated carcinogenic or cocarcinogenic effect. The most common tumors induced by metals are those of the lung. Arsenic induces cancer of the lung and skin, beryllium may induce lung cancer, the effects of cobalt are dubious, cadmium can induce cancer of the lung and, above all, prostate, the role of iron is uncertain, hexavalent chrome may induce cancer of the lung and nasal fossae, nickel is responsible for cancer of lung and nasal fossae. Our understanding of metal carcinogenesis is clearly insufficient and more experimental research and epidemiologic studies addressing this subject are needed.
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PMID:[Carcinogenic effect of metals]. 631 79

Histological examination of serial sections from 127 cases of precancerous lesions and 86 cases of early cancer of the vocal cords was conducted. A histological precancerous state was observed: cellular dysplasia. Analysis of progression of cancer of the vocal cords showed 4 different varieties of carcinogenesis: one sudden, one progressive, one by proliferation and one by transformation. Functional conservative surgery of a glottic cancer had been performed in 76.7 p. cent of cases, and cobalt therapy applied in 23.3 p. cent. Recurrence rate was 6.1 p. cent after surgery and 30.0 p. cent after irradiation. Recovery occurred in 75.6 p. cent after surgery and 65.0 p. cent after irradiation. Precancerous lesions were treated by conservative operations and by microsurgery.
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PMID:[Clinical and anatomopathological course of cancer starting in the vocal cords. Results of treatment]. 684 67

Crystalline nickel sulfide (alpha NiS) and cobalt sulfide (CoS2) particles can cause greater cell transformation and cellular toxicity than the respective amorphous metal sulfide particles. Cultured mammalian cells phagocytose the crystalline metal sulfide particles more readily than the amorphous ones. In the case of the nickel sulfides, the crystalline metal sulfide particles had negatively charged surfaces (Zeta potential: -27.012 mV) in contrast to the amorphous particles, which were positively charge (Zeta potential: +9.174 mV). X-ray photoelectron spectroscopy analysis of amorphous and crystalline NiS particles revealed that the outermost surface (1-4 nm) of the two particles had striking differences in Ni/S ratios and in their sulfur oxidation states. Rendering particles' surfaces more negative by reduction with lithium aluminum hydride enhanced their phagocytosis, and in the case of amorphous NiS chemical reduction resulted in an incidence of morphological transformation of Syrian hamster embryo cells comparable to that observed with untreated crystalline alpha NiS.
Carcinogenesis 1982
PMID:The phagocytosis and transforming activity of crystalline metal sulfide particles are related to their negative surface charge. 706 46


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