Risk factors for breast cancer

Lewis, Peter J.

doi:10.1136/bmj.310.6989.1270b

Cited by 3 publications

(4 citation statements)

References 3 publications

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“…1A) unless they were simultaneously perfused with phorbol 12-myristate 13-acetate (Fig. 1B), which is known to activate hepatic macrophages (Kupffer cells) (25,26 (Fig. 2A).…”

Section: Resultsmentioning

confidence: 99%

Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma.

Hagen

Huang

Curnutte

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

283

190

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A transgenic mouse strain that expresses the hepatitis B virus (HBV) large envelope protein in the liver was used to determine the extent of oxidative DNA damage that occurs during chronic HBV infection. This mouse strain develops a chronic necroinflammatory liver disease that mimics the inflammation, cellular hyperplasia, and increased risk for cancer that is evident in human chronic active hepatitis. When perfused in situ with nitroblue tetrazolium, an indicator for superoxide formation, the liver of transgenic mice displayed intense formazan deposition in Kupffer cells, indicating oxygen radical production, and S-phase hepatocytes were commonly seen adjacent to the stained Kupffer cells. Similar changes were not observed in nontransgenic control livers. To determine whether these events were associated with oxidative DNA damage, genomic DNA from the livers of transgenic mice and nontransgenic controls was isolated and examined for 8-oxo-2'-deoxyguanosine, an oxidatively modified adduct of deoxyguanosine. Results showed a significant, sustained accumulation in steady-state 8-oxo-2'-deoxyguanosine that started early in life exdusively in the transgenic mice and increased progressively with advancing disease. The most pronounced increase occurred in livers exhibiting microscopic nodular hyperplasia, adenomas, and hepatocellular carcinoma. Thus, HBV transgenic mice with chronic active hepatitis display greatly increased hepatic oxidative DNA damage. Moreover, the DNA damage occurs in the presence of heightened hepatocellular proliferation, increasing the probability of fixation of the attendant genetic and chromosomal abnormalities and the development of hepatocellular carcinoma.Chronic inflammatory diseases affect millions of people world-wide and may be a primary factor in the development of up to one-third of all cancers (1). A major association between a persistent infection and cancer is evident in chronic active hepatitis B virus (HBV) infection (2). Epidemiological studies show that incidence of hepatocellular carcinoma (HCC) correlates strongly to geographical areas of endemic HBV infection (3). Furthermore, patients with chronic hepatitis have a much higher incidence of liver cirrhosis and HCC than individuals not infected with HBV (4). Also, HBV antigens in sera of patients are associated with HCC (5). Because the virus infects >300 million people throughout the world, HBV has been described as second only to tobacco as a known human carcinogen (6).Despite the apparent epidemiological association of chronic active hepatitis infection and cancer, the mechanisms involved are still not entirely understood. Research has been hampered due to the long latency period between the onset of infection and cancer development, and the lack of suitable animal models that mimic chronic active human hepatitis.HBV does not contain any known acutely transforming oncogenes, and only rarely do integrated HBV sequences activate cellular protooncogenes (7-10). In contrast, persistent inflammation associated with chro...

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“…1A) unless they were simultaneously perfused with phorbol 12-myristate 13-acetate (Fig. 1B), which is known to activate hepatic macrophages (Kupffer cells) (25,26 (Fig. 2A).…”

Section: Resultsmentioning

confidence: 99%

Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma.

Hagen

Huang

Curnutte

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

283

190

View full text Add to dashboard Cite

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“…In renal fibrosis, there is increasing evidence demonstrating the roles for MMP-9 and MMP-2 in degradation of denatured collagens, fibronectin, laminin, elastin, and vitronectin 81 , 82 . They are also involved in the ECM remodeling 83 , 84 . Moreover, MMP-9 and MMP-2 have been suggested to induce fibrosis through TGF-β1 (a crucial mediator of fibrogenesis) and collagen-degrading proteases 83 , 84 .…”

Section: Discussionmentioning

confidence: 99%

“…They are also involved in the ECM remodeling 83 , 84 . Moreover, MMP-9 and MMP-2 have been suggested to induce fibrosis through TGF-β1 (a crucial mediator of fibrogenesis) and collagen-degrading proteases 83 , 84 . Since the increase in MMP-9 activity was more striking than that of MMP-2 in our present study, it was thus plausible that MMP-9 was more predominant than MMP-2 in driving renal fibrosis mediated by COM-MP secretome.…”

Section: Discussionmentioning

confidence: 99%

Effects of secretome derived from macrophages exposed to calcium oxalate crystals on renal fibroblast activation

et al. 2021

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The association between kidney stone disease and renal fibrosis has been widely explored in recent years but its underlying mechanisms remain far from complete understanding. Using label-free quantitative proteomics (nanoLC-ESI-LTQ-Orbitrap MS/MS), this study identified 23 significantly altered secreted proteins from calcium oxalate monohydrate (COM)-exposed macrophages (COM-MP) compared with control macrophages (Ctrl-MP) secretome. Functional annotation and protein-protein interactions network analysis revealed that these altered secreted proteins were involved mainly in inflammatory response and fibroblast activation. BHK-21 renal fibroblasts treated with COM-MP secretome had more spindle-shaped morphology with greater spindle index. Immunofluorescence study and gelatin zymography revealed increased levels of fibroblast activation markers (α-smooth muscle actin and F-actin) and fibrotic factors (fibronectin and matrix metalloproteinase-9 and -2) in the COM-MP secretome-treated fibroblasts. Our findings indicate that proteins secreted from macrophages exposed to COM crystals induce renal fibroblast activation and may play important roles in renal fibrogenesis in kidney stone disease.

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“…A on the cytotoxic properties of H202 and Blm has been undertaken number of investigations into the biochemical and biological with human leukaemia cells (HL-60) and with the microfeatures of oxidative stress have utilized H202 as a model oxidant organism, Euglena gracilis. Each of these systems has the [6][7][8][9][10][11][12][13]. H202 causes lipid peroxidation [7], DNA damage advantage that cells can be cultured in chemically defined media, [6][7][10][11][12], and cell killing [6][7][8][9][10]12,13].…”

Section: Introductionmentioning

confidence: 99%

Iron requirement for cellular DNA damage and growth inhibition by hydrogen peroxide and bleomycin

Radtke

Lornitzo

Byrnes

et al. 1994

Biochemical Journal

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Studies with Euglena gracilis and HL-60 cells have assessed the need for intracellular iron in the mechanisms of inhibition of cell growth and DNA damage by H2O2 and bleomycin. Cell culture media were directly depleted of iron in order to deprive cells of nutrient iron. Major pools of cellular iron were reduced in both cell types. Nevertheless, iron bound in e.s.r.-observable haem protein and ribonucleotide diphosphate reductase in HL-60 cells was not decreased. In both control cell populations, there was a concentration-dependent reduction in proliferation and cell survival caused by H2O2. In comparison, the proliferation rates of both iron-deficient cell types were significantly less sensitive to H2O2. H2O2 caused concentration-dependent single-strand breakage in DNA in control HL-60 and Euglena gracilis cells. Iron deficiency reduced the amount of strand breaks in HL-60 cells at each concentration of H2O2 used. Single-strand breakage caused by H2O2 in Euglena gracilis was a direct function of the concentration of iron in which the cells had been grown. Growth inhibition and both single- and double-strand DNA damage caused by bleomycin were substantially reduced or eliminated in iron-deficient cells. Copper bleomycin behaved like metal-free bleomycin when assayed for the capacity to cause DNA damage in iron-normal and iron-deficient HL-60 cells. In contrast, iron bleomycin was equally active under the two conditions in these cells.

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Risk factors for breast cancer

Cited by 3 publications

References 3 publications

Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma.

Extensive oxidative DNA damage in hepatocytes of transgenic mice with chronic active hepatitis destined to develop hepatocellular carcinoma.

Effects of secretome derived from macrophages exposed to calcium oxalate crystals on renal fibroblast activation

Iron requirement for cellular DNA damage and growth inhibition by hydrogen peroxide and bleomycin

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