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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuroendocrine lung cancers can be induced in hamsters within 8-12 weeks by combined exposure to N-nitrosodiethylamine (DEN) and hyperoxia. The expression of the c-Ki-ras gene in this lung cancer model was studied using polymerase chain reaction analysis of mRNA (RNA/PCR). We used four different groups of hamsters, exposed for 6 weeks to DEN with hyperoxia (60% oxygen), DEN, hyperoxia, or ambient air, respectively. Total RNA was isolated from lung tissues and cDNA made prior to PCR amplification. A 234-bp product was amplified from c-Ki-ras cDNA and quantitated using scanning laser densitometry. The data obtained were normalized to the expression of the house keeping gene B-actin. The c-Ki-ras products were present after amplification of all hamster lung RNA samples. The hamster lungs exposed to DEN with hyperoxia displayed higher c-Ki-ras protooncogene expression than hamsters exposed to DEN, hyperoxia, or ambient air alone. Since the animals studied were sacrificed at 6 weeks, prior to the appearance of tumors, we conclude that this increased expression may indicate a role for c-Ki-ras in the initial steps in malignant transformation of neuroendocrine cells.
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PMID:Increased c-Ki-ras expression in hamster lung exposed to N-nitrosodiethylamine and hyperoxia as detected by the polymerase chain reaction. 171 35

Exposure to hyperoxia has been demonstrated to alter the cell number of lung fibroblasts in vivo. The precise mechanism of lung fibroblast proliferation after hyperoxic exposure has not been elucidated, however. We examined the growth characteristics of lung fibroblasts isolated from 21-day-old rats exposed to air or 100% O2 for 8 days. Cell proliferation was assessed by hemocytometry, [3H]thymidine incorporation, and fractional labeling with the thymidine analog bromodeoxyuridine. Under all conditions tested, fibroblasts isolated from O2-exposed rats grew more rapidly than those from air-exposed rats. Conditioned medium from fibroblasts isolated from hyperoxia-exposed rats failed to increase the [3H]thymidine incorporation of control cells to that observed in cells isolated from hyperoxia-exposed animals, suggesting that an autocrine growth factor was not responsible for the excess proliferation. Sensitivity to exogenous growth factors was assessed by measuring the response to increasing concentrations of insulin-like growth factor-1 (IGF-1). Relative to 1% fetal bovine serum (FBS), concentrations of IGF-1 between 3 and 30 ng/ml significantly increased the [3H]thymidine incorporation of fibroblasts derived from hyperoxic animals, whereas control cells were unresponsive to IGF-1 stimulation. The apparent sensitivity to IGF-1 led us to assess the effect of in vivo hyperoxic exposure on the expression of c-Ha-ras, which encodes a membrane-bound, GTP-binding/hydrolyzing protein essential for progression through G1 in the cell cycle. ras mRNA levels in quiescent, control cells were minimal but increased following serum stimulation. The c-Ha-ras expression of lung fibroblasts from hyperoxia-exposed animals, on the other hand, was substantial in quiescent cells and remained high after serum exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo hyperoxic exposure increases cultured lung fibroblast proliferation and c-Ha-ras expression. 781 67

Treatment of hamsters with nitrosamines and hyperoxia (60% O2) induces neuroendocrine lung tumors. Analysis of 8 different tumors from 7 different hamsters demonstrated 2- to 3.5-fold increases in the expression of c-myc in 4 of 8 tumors, c-fos in 3 tumors, c-jun in 1 tumor, c-raf in 1 tumor, and Ki-ras in 2 tumors. No overexpression of the c-src and Ha-ras gene transcripts were detected. Expression levels of N-myc, p53 and the retinoblastoma gene transcript were too low to be quantitated accurately. In some cases, slightly elevated levels of protooncogene transcripts (less than 2-fold) were detected in normal-appearing tissue isolated from the same tumor bearing hamsters. Hyperoxia alone had little effect on the expression of c-myc or c-fos RNA transcripts compared to untreated hamsters. Reverse transcription of the RNAs and amplification of the cDNA copies by the polymerase chain reaction, followed by selective oligonucleotide hybridization with normal and mutant probes, did not reveal any mutations in the 12th, 13th, or 61st codons of the seven tumors which produced Ki-ras cDNA. An additional 8 tumors were also screened for Ki-ras mutations following amplification of genomic DNA and demonstrated an absence of point mutations at the Ki-ras gene locus. These results indicate that the hamster neuroendocrine lung tumors exhibit slight increases in c-myc and c-fos RNA expression but lack mutations at the Ki-ras gene locus.
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PMID:Molecular characterization of neuroendocrine lung-tumors induced in hamsters by treatment with nitrosamines and hyperoxia. 2156 81