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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of hyperoxia on lung tumor development were examined in mice and rats. In mice, exposure to 70% O2 prevented the development of urethan- or 3-methylcholanthrene-induced lung tumors. Dietary antioxidants [butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA)] were unable to prevent the inhibition of tumor development by oxygen, although BHT retained its capability to enhance tumor development in mouse lung. In visible-size tumors, oxygen did not depress DNA synthesis. Oxygen also reduced the number of pulmonary metastatic nodules after i.v. injection of mammary gland-derived carcinoma cells, but failed to inhibit growth of murine lung carcinoma or murine melanoma-derived cell lines. Rats treated with one single intratracheal instillation of 3-methylcholanthrene developed multiple lung lesions; their growth could be prevented by exposure of the animals to 40 or 70% O2. It is concluded that hyperoxia prevents development of transformed cells in vivo in the lung and may affect adversely the growth of selected cell lines metastatic to the lung.
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PMID:Modification of lung tumor growth by hyperoxia. 374 30

The hypothesis was tested that continuous hyperoxia would enhance the development of lung tumors in mice. In strain A/J mice treated with a single dose of urethan (1000 mg/kg) and exposed to 70% O2 for 16 wk, an average of 5 tumors per lung developed, whereas in animals kept in air, an average of 20 tumors per lung was found. When the animals were returned to air after oxygen exposure, it was found that a difference of 15 tumors per lung between the two groups persisted up to 1 yr later, indicating that O2 was tumoricidal. The shortest duration of O2 exposure to be effective was 4 wk, and delay of O2 exposure up to 12 wk after urethan still was effective in reducing the number of developing tumors. Histopathology showed that continued exposure to 70% O2 produced some hyperplasia of the bronchiolar epithelium and only very discrete changes in the pulmonary parenchyma. Analysis of cell proliferation patterns with a continuous [3H]thymidine labeling technique showed a persistent high cell labeling in the bronchiolar epithelium and a temporary increase in alveolar wall cell labeling. Chronic hyperoxia failed to alter the activities of pulmonary superoxide dismutase or glucose-6-phosphate dehydrogenase. Ornithine decarboxylase, on the other hand, was increased as long as the animals remained exposed to oxygen. It was concluded that hyperoxia kills developing tumor cells in mouse lung.
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PMID:Inhibition of mouse lung tumor development by hyperoxia. 394 76

Tumor oxygenation during respiratory hyperoxia is dependent on the tumor growth site, on the growth stage, and hence on the vascular pattern. Diffusion of O2 from the surrounding atmosphere contributes considerably to the oxygenation of subcutaneous tumors during normobaric exposure to a pure O2 atmosphere. However, hypoxia is still present in the tumor core under these conditions, and pressurization up to 4 bar is required to completely eradicate these hypoxic areas, thus enhancing the radiosensitivity of the tumors.
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PMID:Effectiveness of respiratory hyperoxia, of normobaric and of hyperbaric oxygen atmospheres in improving tumor oxygenation. 673 Nov 16

Pulmonary fibroblasts exposed to hyperoxic conditions in vitro release factors into their culture medium which influence the growth and lipid synthesis of tumor and nontumor pulmonary epithelial cells, but not pulmonary fibroblasts. These factors may be either inhibitory or stimulatory, depending on the degree and duration of hyperoxic exposure. Two stimulatory heat-labile factors have been tentatively identified by gel filtration. A growth-stimulating factor induced by hyperoxia has an apparent molecular weight approximately 20,000-26,000 daltons; a factor tht stimulates lipid synthesis has an apparent molecular weight approximately 8000 daltons. These factors appear distinct from other pneumocyte-specific peptides which occur in response to steroid therapy or pneumonectomy.
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PMID:Cellular interactions in pulmonary oxygen toxicity in vitro: I. Hyperoxic induction of fibroblast factors which alter growth and lipid metabolism of pulmonary epithelial cells. 687 99

Experiments were performed to determine whether changes in T2*-weighted MR images during and after hyperoxia differentiate tumors from normal tissue. Mammary adenocarcinomas implanted in the right hind limbs of rats were studied. Gradient echo images were obtained at 2 Tesla with an evolution time of 20 ms and a recycle time of 1 s. Breathing gas was either air or 100% O2. Significant increases in image intensity were observed in tumor centers and rims during hyperoxia while much smaller changes were detected in the surrounding muscle. The relaxation rate (1/T2*) in tumors decreased during hyperoxia by an average of 2.5 +/- 1.0 s-1, while in muscle the average change was an increase of 0.6 +/- 2.1 s-1. The largest decreases in relaxation rate were detected in non-necrotic tumor regions with relatively low density of blood vessels. Immediately following hyperoxia significant decreases in intensity were detected in tumors while much smaller decreases were detected in the surrounding muscle.
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PMID:Changes in T2*-weighted images during hyperoxia differentiate tumors from normal tissue. 776 Jul

Reactive oxygen species produced by normal cellular metabolism have been considered to play a causative role in spontaneously occurring genomic instability and carcinogenesis. To study the genotoxic consequences of an enhanced flux of metabolically produced reactive oxygen species, cells may be exposed to hyperoxia (elevated concentrations of oxygen), a condition known to generate high levels of microscopically visible chromosomal damage. Here we assess the mutagenic potential of normobaric hyperoxia in several mammalian cells lines (CHO-K1-BH4 and AS52 Chinese hamster cells and TK6 human lymphoblastoid cells) using different target genes, including hprt, xprt and tk. Exposure of cell cultures to hyperoxia to 10-40% clonogenic cell survival, failed to induce mutations at the hprt and xprt loci. In human TK6 cells, hyperoxia failed to induce normal growing tk mutants, but efficiently induced slow growing tk mutants. The latter type of mutant is supposed to result from very large deletions or mutlilocus events. Our results suggest that elevated levels of endogenous activated oxygen species are inefficient in inducing point mutations or small deletions, but tend to generate gross rearrangements. Mammalian cells under oxidative stress thus exhibit a hyper-recombination phenotype. The carcinogenic impact of metabolic oxygen radical fluxes may thus be based on enhanced mitotic recombination rates, leading to tumor suppressor gene inactivation through 'loss of heterozygosity'.
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PMID:Mutagenicity of metabolic oxygen radicals in mammalian cell cultures. 800 Dec 23

Experiments were performed to determine whether T2* and resonance frequency weighted MR images are sensitive to effects of hyperoxia on model tumors. Hyperoxia can increase tumor oxygen tension and thus affect T2* and/or the average resonance frequency within each image voxel due to the paramagnetism of oxygen itself or through modulation of the oxidation state of hemoglobin. Alternatively, changes in T2* during hyperoxia may reflect changes in tumor water content due to changes in systemic blood pressure. Mammary adenocarcinomas implanted in the flanks of rats were studied. Imaging sequences were preceded by two 90 degrees pulses separated by an evolution period of 50 or 75 ms and followed by a crusher gradient to eliminate transverse magnetization. This pulse sequence produced images which were sensitized to both T2* and the average resonance frequency of each voxel. Images were produced at 2 T using a gradient echo imaging method with a TR of 3 s. Images obtained during inhalation of air and 100% O2 were compared. Significant increases in image intensity were observed in most tumors during hyperoxia, particularly at the tumor center. The increase was accentuated when the evolution period was increased and greatly reduced when a 180 degrees refocusing pulse was placed at the center of the evolution period. These results suggest that hyperoxia reduces local magnetic susceptibility gradients leading to an increase in T2* or causes a shift in resonance frequency. The magnitude of this change may be a function of the rate at which oxygen is delivered to and metabolized by tumors and may also reflect tumor oxygen tension under normoxic conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of hyperoxia on T2* and resonance frequency weighted magnetic resonance images of rodent tumours. 806 23

We tested the hypothesis that the two common oxidant air pollutants, ozone and nitrogen dioxide, modulate the development of respiratory tract tumors in Syrian golden hamsters. The animals received subcutaneous injections of the carcinogen diethylnitrosamine (20 mg/kg) twice a week while being exposed continuously to an atmosphere of 0.8 parts per million (ppm)* of ozone or 15 ppm of nitrogen dioxide. Animals were killed 16 weeks or 24 to 32 weeks after the beginning of the treatment. Ozone delayed the appearance of tracheal tumors and reduced the incidence of tumors in the lung periphery. A suspected neuroendocrine differentiation of those lung tumors could not be established by immunocytochemistry due to overfixation of tissues. On the other hand, ozone seemed to mitigate development of hepatotoxic lesions mediated by diethylnitrosamine. In animals treated with diethylnitrosamine and exposed to nitrogen dioxide, fewer tracheal tumors and no lung tumors were found. Only a few lung tumors were produced in animals treated with diethylnitrosamine and kept in an atmosphere of 65% oxygen. The previously observed neuroendocrine nature of tumors induced by simultaneous exposure to diethylnitrosamine and hyperoxia could not be established because the long fixation of tissues precluded immunocytochemical stains. Animals treated with diethylnitrosamine and kept in filtered air while being housed in wire-mesh cages developed fewer lung tumors than animals given the same treatment and kept on conventional bedding in shoebox cages. Although all inhalants tested are known to produce substantial cell proliferation in the respiratory tract, it was not possible to document whether this would enhance lung tumor development. The role of the two common air pollutants, ozone and nitrogen dioxide, as possible additional risks in the pathogenesis of lung cancer in animals continues to remain uncertain.
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PMID:Failure of ozone and nitrogen dioxide to enhance lung tumor development in hamsters. 821 71

A variety of treatments that modulate tumor oxygen tension are used clinically to improve the outcome of radiotherapy. High resolution, noninvasive measurements of the effects of these treatments would greatly facilitate the development of improved therapies and could guide treatment of cancer patients. Previous work demonstrated that magnetic resonance (MR) gradient echo imaging of the water proton resonance detects changes in T2* and T1 in tumors during hyperoxia that may reflect increased tumor oxygenation. This report describes the use of high resolution MR spectroscopic imaging with short repetition time (TR = 0.2 s) to improve the accuracy with which changes in T2* and T1 are measured. Mammary adenocarcinomas grown in the hind limbs of rats were studied. Carbogen inhalation was used to induce hyperoxia. A single 2-mm slice through the center of tumors and underlying muscle was imaged at 4.7 Tesla with in-plane resolution of approximately 1.2 mm and frequency resolution of 5.8 Hz. The peak integral increased by an average of 6% in tumors during carbogen inhalation suggesting a decrease in T1 (n = 8, P < 0.001). Peak height increased by an average of 15% in tumors during carbogen inhalation (n = 8, P < 0.001). The large difference between increases in peak height and peak integral demonstrates that the width of the water resonance decreased. Assuming a Lorentzian lineshape, an average increase of 12% in T2* was observed in tumors. In muscle, peak integral and peak height increased slightly (about 1.2% and 3%, respectively; P < 0.02) during carbogen inhalation but no significant change in T2* was observed. Spectroscopic imaging detects changes in the water proton resonance in tumors during hyperoxia accurately and reproducibly with high signal-to-noise ratio and allows clear separation of T1 and T2* effects. Increases in T2* may be due to decreased deoxyhemoglobin in tumor blood vessels (i.e., the BOLD effect) and may provide a clinically useful index of increases in tumor oxygenation.
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PMID:Spectroscopic imaging of the water resonance with short repetition time to study tumor response to hyperoxia. 921 76

We hypothesized that manganese superoxide dismutase (MnSOD), known to be induced in rat mesothelial cells by asbestos fibers, cytokines, and hyperoxia, may also be induced in asbestos-related pleural diseases such as mesothelioma. MnSOD was assessed in healthy human pleural mesothelium (n = 6), in biopsy samples of human pleural mesothelioma (n = 7), in transformed nonmalignant human mesothelial cells (Met5A), and in two human mesothelioma cell lines (M14K and M38K) established from the tumor tissue of mesothelioma patients. There was no MnSOD immunoreactivity in five of the six samples of healthy pleural mesothelium, whereas MnSOD immunoreactivity was high in the tumor cells in all the mesothelioma samples. Northern blotting, immunohistochemistry, Western blotting, and specific activity measurements showed lower MnSOD in the nonmalignant Met5A mesothelial cells than in the M14K and M38K mesothelioma cells. In additional experiments the mesothelial and mesothelioma cells were exposed to menadione, which generates superoxide intracellularly, and to epirubicin, a cytotoxic drug commonly used to treat mesothelioma. The M38K mesothelioma cells were most resistant to menadione and epirubicin when assessed by LDH release or by adenine nucleotide (ATP, ADP, and AMP) depletion. These same cells showed not only the highest MnSOD levels, but also the highest mRNA levels and activities of catalase, whereas glutathione peroxidase and glutathione reductase levels did not differ significantly. We conclude that MnSOD expression is low in healthy human pleural mesothelium and high in human malignant mesothelioma. The most resistant mesothelioma cells contained coordinated induction of MnSOD and catalase.
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PMID:Manganese superoxide dismutase in healthy human pleural mesothelium and in malignant pleural mesothelioma. 953 46


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