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

Radiation damage in phospholipid membranes involves free radical chain reactions which propagate on their own. These reactions oxidize the constituent fatty acids (LH) to alkyl radicals (L) which upon oxygenation, for lipid hydroperoxides (LOOH), some of which absorb light at 232 nm. The response (R) of these membranes to irradiation from tritium (3H) in tritiated water increases with dose (D) in accordance with R = aDm, where m = 1.44 +/- 0.30 in the absence of superoxide dismutase and 0.80 +/- 0.14 in its presence. The parameter "a" is expressible in terms of dose rate (delta D/delta t) by a = c (delta D/delta t)-n, where n = 1.18 +/- 0.05 in the absence of superoxide dismutase and 0.82 +/- 0.02 in its presence. Thus, R = cDm(delta D/delta t)-n where the values of m, n depend on the presence or absence of the free radical scavenger, superoxide dismutase. From this composite relationship, the response per annum for 100-250 millirem/y is calculable and found to differ qualitatively, that is, in the absence of superoxide dismutase the response increases whereas in the enzyme's presence it decreases. The latter trend is reminiscent of the correlation between radiation dose rate and the per annum malignant rate in humans. This coincidence is interesting in that LOOH are linked in the literature to several forms of carcinogenesis.
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PMID:Radiation carcinogenesis from a membrane perspective. 693 8

DNA repair after gamma radiation was studied in purified T lymphocytes from young and aged subjects. Two different assays were employed. In the first, T lymphocytes were stimulated with phytohemagglutinin (PHA) for 72 h and then treated with hydroxyurea, irradiated with 30 K rads and pulsed with [3H]thymidine (TdR) for 4 h. In the second, T lymphocytes were first irradiated with graded doses of gamma rays (200-800 rads) and then stimulated with PHA, cultured for 72 h and pulsed with 3H-TdR for the last 6 h of culture. T lymphocytes from aged subjects showed a lack of DNA repair synthesis in the first assay whereas only minor differences were found in the second assay between the two groups, i.e., a certain degree of radioresistance in aged lymphocytes. Lymphocyte superoxide dismutase activity showed great individual variations in both groups and a slight increase in old subjects.
Carcinogenesis 1982
PMID:DNA repair after gamma radiation and superoxide dismutase activity in lymphocytes from subjects of far advanced age. 697

The induction of sister chromatid exchanges (SCE) by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was measured in mouse 10T1/2 and 3T3 cells released from density; inhibition, and Chinese hamster CHO cells synchronized by mitotic selection. The induced frequency of SCE was similar in each cell type, but depended upon the concentration of TPA employed, its source, and the particular lot from the same source. Most SCE occurred in the first two rounds of cell replication after addition of TPA. The induction of SCE by TPA was markedly suppressed if the fetal calf serum in the incubation medium was not heat-inactivated. The addition of superoxide dismutase to medium with heat-inactivated serum also suppressed the induction of SCE. These results suggest that free radicals, particularly the superoxide anion, may be important intermediates in some of the biologic effects of TPA.
Carcinogenesis 1981
PMID:Factors influencing the induction of sister chromatid exchanges in mammalian cells by 12-O-tetradecanoyl-phorbol-13-acetate. 727 39

The effects of phorbol ester tumor promoters and related compounds on superoxide dismutase (SOD) and catalase were examined. The treatment of adult mouse skin with 2 micrograms 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in a sustained decrease in the basal levels of both SOD and catalase activities in the epidermis. A decline in SOD activity occurred within 3 h after application and the maximum effect was seen at 16--17 h. The decrease in SOD activity was always accompanied by a similar decline in the epidermal catalase activity. The alterations in both enzymes occurred against a high background of enhanced protein synthesis which indicates that the effect of TPA is selective for SOD and catalase. Other tumor promoters such as phorbol 12,13-dibutyrate and the non-phorbol tumor promoter anthraline also lowered the activities of both the enzymes. Mezerein, a resiniferonol derivative with weak promoting activity but a potent stage-II promoter, appeared to be more potent than TPA in lowering the basal levels. These results indicate that damage which favors neoplastic progression could occur in TPA-treated mouse skin due to the accumulation of free radicals resulting from low levels of SOD and catalase activity. In addition, the TPA-caused decrease in the levels of SOD and catalase was not prevented by either retinoic acid, fluocinolone acetonide, tosyl amino-2-phenylethyl chloromethyl ketone, or butylated hydroxytoluene, suggesting that inhibition of tumor promotion by these agents is not mediated through alterations in the levels of enzymatic activities which decrease free radical concentrations.
Carcinogenesis 1981
PMID:Diminution of mouse epidermal superoxide dismutase and catalase activities by tumor promoters. 731 51

The authors have studied DNA base damage and activities of antioxidant enzymes in human benign prostatic hyperplasia (BPH) tissues and surrounding disease-free tissues removed from prostate glands of 15 patients. In these tissues, endogenous levels of various typical hydroxyl radical-induced products of DNA bases and activities of catalase and superoxide dismutase were measured. The majority of patients had higher levels of DNA base lesions and lower activities of enzymes in BPH tissues than in normal prostate tissues. When activities of both enzymes were lower in BPH tissues than in normal tissues, the increases in the amounts of DNA base lesions over control levels were most prominent. In the case of similar enzyme activities in both BPH and normal tissues, no changes in levels of DNA base lesions were observed. These results suggest a possible association between antioxidant enzyme activities and levels of DNA base lesions in BPH tissues. Some of the identified DNA lesions are known to be premutagenic and may play a role in carcinogenesis. Although a possible link between BPH and prostate cancer is controversial, BPH patients with both decreased antioxidant enzyme activities and increased levels of DNA lesions may be at risk of developing prostate cancer.
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PMID:DNA base modifications and antioxidant enzyme activities in human benign prostatic hyperplasia. 753 80

Incubation of chromium(VI) [Cr(VI)] with cultured Jurkat cells resulted in activation of DNA binding activity of the nuclear factor (NF)-kappa B. In a combination with glutathione reductase, a Cr(VI) reducing agent, Cr(VI) expressed an enhanced activity in induction of NF-kappa B. This activation of NF-kappa B was decreased by a metal chelator, diethylene-triaminepentaacetic acid or catalase, but increased by superoxide dismutase. Addition of Mn2+, which reacts with Cr(IV) and inhibits Cr(IV)-mediated hydroxyl radical (.OH) generation via Fenton-like reaction, attenuated the activation of NF-kappa B. Sodium formate, an .OH radical scavenger, also inhibited the activation. Electron spin resonance measurements showed that the incubation of Cr(VI) with intact Jurkat cells generated reactive Cr(V) intermediate. Glutathione reductase and NADPH enhanced Cr(V) generation. Electron spin resonance spin trapping measurements using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trapping agent provided evidence that the incubation of Cr(VI) with the Jurkat cells in the presence of glutathione reductase generated .OH radicals. H2O2 enhanced .OH radical generation and also enhanced Cr(V) formation, indicating the role of Cr(IV) in .OH radical generation. We conclude that Cr(VI) can activate NF-kappa B in vitro via Cr(IV)-mediated free radical reactions. We hypothesize that Cr(VI)-mediated NF-kappa B activation may be involved in the mechanism of Cr(VI)-induced carcinogenicity.
Carcinogenesis 1995 Oct
PMID:Chromium(VI)-induced nuclear factor-kappa B activation in intact cells via free radical reactions. 758 42

Recent studies from this laboratory have shown that asbestos fibers are mutagenic in cultured mammalian cells when assayed using a system that can detect multilocus deletions. Southern analysis of the induced mutants shows that the majority contain large deletions ranging in size from a few thousand to several million basepairs. In the present study, the effects of free radical scavenging enzymes on the cytotoxic and mutagenic potential of chrysotile fibers were examined using the human-hamster hybrid (AL) cells. Exponentially growing cells were treated with graded doses of fibers for a 24 h period either in the presence or absence of catalase, superoxide dismutase (SOD) or Tempol. Fiber-exposed cells were treated with the various enzymes either concurrently with the fiber or extended through the entire expression period. While the survival of AL cells treated with graded doses of chrysotile fibers with or without a concurrent treatment with SOD and catalase was not significantly different, the mutation yield at the S1 locus was significantly reduced in cells treated with these antioxidant enzymes. Furthermore, cells treated with the enzymes for a prolonged period were not better protected than those treated only during fiber treatment. The SOD mimic nitroxide, Tempol, had no effect on either the survival or mutagenic yield of chrysotile fibers. While SOD and catalase reduced the mutagenic potency of asbestos fibers in AL cells, they did not alter the molecular spectrum of fiber-induced mutagenesis. Our results indicate that antioxidant enzymes can protect cells against the genotoxic damages induced by chrysotile fibers, and are highly suggestive of the roles of oxyradicals in the fibrogenic and carcinogenic mechanisms of asbestos fibers.
Carcinogenesis 1995 Jul
PMID:Effects of antioxidants on fiber mutagenesis. 761 91

In this work comprehensive data of antioxidant enzymes are reviewed and their role in carcinogenesis is discussed. When compared to their normal tissue counterparts, more of the tumor tissues were low in Cu, Zn-SOD and catalase activity and in some cases in Mn-SOD. It is probably characteristic for tumor tissues. Glutathione peroxidase, and glutathione reductase and glucose-6-phosphate dehydrogenase activities are highly variable. The reason why cancerous cells exhibit abnormal levels and activities of antioxidant enzymes is unknown. It was hypothesized, that during formation of the tumor, by certain obscure mechanism, cells with imbalance of antioxidant enzymes profile were selected over normal cells. It is not known whether the changes in antioxidant defence observed in cancerous tissues play a role in carcinogenesis, or are formed as a results of the disease.
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PMID:[Activity of antioxidant enzymes in cancer diseases]. 763 95

Several tumour promoting chemicals have been shown to inhibit intercellular communication (IC) through gap junctions in cell cultures. In the present investigation we studied the effect of the hepatic tumour promoters phenobarbital (PB), 1,1,1-trichloro-2,2-(p-chlorophenyl)ethane (DDT) and gamma-hexachlorocyclohexane (lindane) on IC in rat hepatocyte cultures. IC was evaluated by microinjection of fluorescent Lucifer Yellow CH dye and visualization of dye spread to adjacent hepatocytes. Incubation of hepatocytes with PB (2 mM), DDT (30 microM) and lindane (25 microM) decreased dye-coupling of the cells by about 30%, 42% and 35%, respectively; dye-coupling in untreated cultures was 88.1 +/- 0.7%. Inhibition of IC was reversible when the xenobiotics were removed from the medium. The antioxidant vitamin E (100 microM) prevented inhibition of dye-coupling by PB and lindane and partially that by DDT. Superoxide dismutase (100 units/microliters) counteracted the effect on dye-coupling by PB, but not that by the insecticides. Similarly, the cyclo-oxygenase inhibitors indomethacin and aspirin only reversed the effect of PB on IC, but not that of DDT or lindane. As indicated by further experiments, prevention by non-steroidal anti-inflammatory agents of PB-induced inhibition of IC is most likely not mediated by inhibition of cyclo-oxygenase. The results indicate significant differences in the action of PB, DDT and lindane on IC in hepatocyte cultures. This is suggested by the differential effects of superoxide dismutase and non-steroidal anti-inflammatory agents on the action of the three tumour promoting chemicals. Whereas superoxide radicals may be involved in the inhibition of dye-coupling by PB, radical intermediates of the insecticides may be responsible for the decrease in dye-coupling by DDT and lindane.
Carcinogenesis 1993 Nov
PMID:Inhibition of intercellular communication in rat hepatocytes by phenobarbital, 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT) and gamma-hexachlorocyclohexane (lindane): modification by antioxidants and inhibitors of cyclo-oxygenase. 769 11

The carcinogenic effects of crystalline silica in rat lungs were extensively demonstrated by many experimental long-term studies, showing a marked predominance for adenocarcinomas originating from alveolar type II cells and associated with areas of pulmonary fibrosis (silicosis). In contrast with its effects in rats, silica did not induce alveolar type II hyperplasia and lung tumors in mice and hamsters, pointing to a critical role for host factors. Using these animal models, we are investigating the role of cytokines and other cellular mediators on the proliferation of alveolar type II cells. Immunohistochemical localization of TGF-beta 1 precursor in alveolar type II cells adjacent to silicotic granulomas was shown to occur in rats, but not in mice, and hamsters, suggesting a pathogenetic role for this regulatory growth factor. Recent investigations in our laboratory on the biologic mechanisms of crystalline silica included determination of anionic sites on crystalline silica surfaces by binding of the cationic dye Janus Green B; binding of crystalline silica to DNA, demonstrated by infrared spectrometry; production of oxygen radicals by crystalline silica in aqueous media; induction of DNA strand breakage and base oxidation in vitro and its potentiation by superoxide dismutase and by hydrogen peroxide; and induction by crystalline silica of neoplastic transformation and chromosomal damage in cells in culture. On the basis of these in vitro studies, we propose that DNA binding to crystalline silica surfaces may be important in silica carcinogenesis by anchoring DNA close to sites of oxygen radical production on the silica surface, so that the oxygen radicals are produced within a few A from their target DNA nucleotides.
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PMID:Mechanisms of carcinogenesis by crystalline silica in relation to oxygen radicals. 770 91


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