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The enzyme DT-diaphorase (DTD; NAD(P)H:quinone oxidoreductase, EC, is an obligate two electron reductase which catalyzes reduction of a broad range of substrates, including quinones. We report here variations in DTD concentrations among different classes of lung tumors known also to vary in their responsiveness to cytotoxic agents. Small cell lung(More)
Human adenocarcinoma (AC) is the most frequently diagnosed human lung cancer, and its absolute incidence is increasing dramatically. Compared to human lung AC, the A/J mouse-urethane model exhibits similar histological appearance and molecular changes. We examined the gene expression profiles of human and murine lung tissues (normal or AC) and compared the(More)
Alterations in the cAMP signal transduction pathway are associated with mouse lung neoplasia, cAMP effects are mediated by activating cAMP-dependent protein kinase isozymes, PKA I and PKA II. E9, a tumorigenic cell line, exhibited decreased PKA I levels compared to C10 cells, a nontumorigenic cell line of similar epithelial origin. Western immunoblots of(More)
Epidemiological investigations suggest that chronic lung inflammation increases lung cancer risk. Pharmacologic and genetic evidence in mouse models indicates that lipid mediators released during pulmonary inflammation enhance lung tumor formation. Cytosolic phospholipase A2 (cPLA2) catalyzes arachidonic acid (AA) release from membrane phospholipids. AA can(More)
The sulfone derivative of the non-steroidal anti-inflammatory drug (NSAID), sulindac, has been reported to inhibit mammary and colon tumor formation in rodent models of chemically-induced carcinogenesis. Unlike its parent compound, this metabolite lacks cyclo-oxygenase inhibitory activity. A tumor induction protocol, consisting of NNK administration in the(More)
Susceptibility to urethane-induced lung adenomas in mice has a polygenic mode of inheritance, with no obvious discontinuity in lung tumour counts among 37 AXB recombinant inbred strains. However, mean tumour counts were markedly higher in strains carrying the A/J allele at the Kras2 and H2 complex than in those carrying the C57BL/ allele. In 162 F2 hybrids(More)
Epidemiologic evidence suggests that pulmonary diseases with a prominent chronic inflammatory component elevate lung cancer risk. Genetic manipulations of mouse models of lung inflammation and tumorigenesis can be used to investigate this association. The genes encoding pro-inflammatory tumor necrosis factor-alpha (TNFalpha) and antiinflammatory IL-10(More)
We examined the responsiveness of normal and neoplastic lung cells to agents which stimulate cAMP production. While their basal cAMP levels were similar, spontaneous in vitro transformant E9 cells and tumor-derived PCC4 cells produced much less cAMP in response to 1 microM isoproterenol compared to non-tumorigenic C10 cells derived from normal mouse lung(More)
Programmed cell death is an active process wherein the cell initiates a sequence of events culminating in the fragmentation of its DNA, nuclear collapse, and disintegration of the cell into small, membrane-bound apoptotic bodies. Examination of the death program in various models has shown common themes, including a rise in cytoplasmic calcium, cytoskeletal(More)
Clara cells were first described as a morphologically distinct cell type by Kolliker in 1881, but they take their name from the seminal study of human and rabbit bronchioles by Max Clara in 1937. Since their discovery, Clara cells have been identified as central players in protecting the airway from environmental exposures. The diverse functions of Clara(More)