Increased c-Ki-ras expression in hamster lung exposed to N-nitrosodiethylamine and hyperoxia as detected by the polymerase chain reaction.
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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Toxic Substances Research and Teaching Program, University of California, Davis 95616.
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Gumerlock
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Witschi
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D000818:Animals; D001483:Base Sequence; D006224:Cricetinae; D004052:Diethylnitrosamine / Q000494:pharmacology*; D004700:Endocrine System Diseases / Q000139:chemically induced / Q000235:genetics; D004801:Eosine Yellowish-(YS); D015870:Gene Expression; D011905:Genes, ras / Q000235:genetics*; D006416:Hematoxylin; D006651:Histocytochemistry; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008175:Lung Neoplasms / Q000139:chemically induced / Q000235:genetics*; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000235:genetics; D009423:Nervous System Neoplasms / Q000139:chemically induced / Q000235:genetics; D010100:Oxygen / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012313:RNA / Q000032:analysis / Q000235:genetics
D004052:Diethylnitrosamine; D012313:RNA; D010100:Oxygen; D004801:Eosine Yellowish-(YS); D006416:Hematoxylin