Tobacco-borne siderophoric activity

Qian, Mingwei; Eaton, John W.

doi:10.1016/0003-9861(89)90374-3

Cited by 27 publications

(17 citation statements)

References 18 publications

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“…The accumulation of iron within test cells was also measured colorimetrically as previously described (8). Briefly, the cells were grown in 100-mm plates under normal culture conditions.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial DNA Damage in Iron Overload

Gao

Campian

Qian

et al. 2009

Journal of Biological Chemistry

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101

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Chronic iron overload has slow and insidious effects on heart, liver, and other organs. Because iron-driven oxidation of most biologic materials (such as lipids and proteins) is readily repaired, this slow progression of organ damage implies some kind of biological "memory." We hypothesized that cumulative iron-catalyzed oxidant damage to mtDNA might occur in iron overload, perhaps explaining the often lethal cardiac dysfunction. Real time PCR was used to examine the "intactness" of mttDNA in cultured H9c2 rat cardiac myocytes. After 3-5 days exposure to high iron, these cells exhibited damage to mtDNA reflected by diminished amounts of near full-length 15.9-kb PCR product with no change in the amounts of a 16.1-kb product from a nuclear gene. With the loss of intact mtDNA, cellular respiration declined and mRNAs for three electron transport chain subunits and 16 S rRNA encoded by mtDNA decreased, whereas no decrements were found in four subunits encoded by nuclear DNA. To examine the importance of the interactions of iron with metabolically generated reactive oxygen species, we compared the toxic effects of iron in wild-type and rho o cells. In wild-type cells, elevated iron caused increased production of reactive oxygen species, cytostasis, and cell death, whereas the rho o cells were unaffected. We conclude that long-term damage to cells and organs in iron-overload disorders involves interactions between iron and mitochondrial reactive oxygen species resulting in cumulative damage to mtDNA, impaired synthesis of respiratory chain subunits, and respiratory dysfunction.Patients with primary or secondary iron overload are liable to cardiac and hepatic failure, and type II diabetes. Iron is required for the activity of numerous iron-and heme-containing proteins, but "free" (i.e. redox active) iron catalyzes the formation of highly toxic reactive oxygen species (ROS) 2 that damage lipids, proteins, and DNA (1). This damage is assumed to arise from iron-catalyzed hydroxyl radical formation or, perhaps more likely, iron-centered radicals such as ferryl and perferryl (2, 3). Iron-driven oxidation events require that the metal interact with cellular oxidizing and reducing equivalents such as superoxide and hydrogen peroxide, a major source of which is "leak" of electrons from the mitochondrial electron transport chain (4 -6).The present investigations were focused on the etiology of iron-mediated cardiac damage and specifically on the question of why, in patients with chronic iron overload, damage to organs such as the heart develops over a period of years, whereas most types of iron-mediated oxidation events can be repaired within minutes or hours. We have investigated the hypothesis that cumulative damage to DNA, specifically mtDNA, is critical to the slow development of cardiac dysfunction in chronic iron overload. In partial support of this idea, earlier studies clearly show that iron does promote DNA base oxidation as well as single and double strand DNA breaks. Mitochondrial DNA may be particularly vulnerable ...

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“…The accumulation of iron within test cells was also measured colorimetrically as previously described (8). Briefly, the cells were grown in 100-mm plates under normal culture conditions.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial DNA Damage in Iron Overload

Gao

Campian

Qian

et al. 2009

Journal of Biological Chemistry

Self Cite

101

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“…The results of our study, shown in Figure 1, can be summarized as follows: (a) MCS was weakly but convincingly clastogenic, and Fe(III) significantly enhanced this effect; (b) the strong clastogenicity of UR was not affected by Fe(III); (c) the clastogenic effect of MCS and UR was much more than additive, and was further enhanced by Fe(III). These data deserve attention because the lungs and alveolar macrophages of smokers contain abnormally large amounts of iron [21], and iron mobilization from ferritin may represent a specific prooxidant mechanism related to cigarette smoking [22].…”

Section: C57bl/6 Micementioning

confidence: 99%

Induction and Modulation of Lung Tumors: Genomic and Transcriptional Alterations in Cigarette Smoke-exposed Mice

Flora

Izzotti

D’Agostini³

et al. 2004

Experimental Lung Research

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Cigarette smoke plays a major role in the epidemiology of lung cancer, and smoke components have extensively been investigated in carcinogenicity and chemoprevention studies in experimental animals. However, it is much more difficult to reproduce the tumorigenicity of the whole complex mixture in preclinical models. The authors review here some results obtained in their laboratories, dealing with the induction of lung tumors, and genomic and transciptional alterations in smoke-exposed mice. The authors were successful in inducing lung tumors in 4 strains of mice exposed whole-body to environmental cigarette smoke, including Swiss albino, A/J, SKH-1 hairless, and p53 mutant (UL533 x A/J)F1 mice. However, the tumorigenic response was rather weak in all strains. Much more intense were the smoke-induced alterations of a variety of intermediate biomarkers, such as cytogenetic end points in pulmonary alveolar macrophages, bone marrow and peripheral blood erythrocytes; apoptosis, p53 oncoprotein, and proliferating cell nuclear antigen in the bronchial epithelium; bulky DNA adducts, 8-hydroxy-2-deoxyguanosine; multigene expression, and thiobarbituric acid-reactive aldehydes in whole lung and several other organs. Smoke-induced genomic and transcriptional alterations were suitable for evaluating their modulation by chemopreventive agent, as shown in studies using the thiol N-acetylcysteine and the nonsteroidal anti-inflammatory drug sulindac.

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“…o-Phenanthroline has been shown (33) to inhibit hydroxyl radical formation and to decrease H202-mediated cell transformation. The organic constituents in CSC also promote the reduction ofiron and its entry into the cells (5,34). Tyrosinase-treated CSC decreased PKC translocation and metastasis, suggesting that the polyphenolic agents present in the CSC may mediate the CSC effects.…”

Section: Resultsmentioning

confidence: 99%

Tobacco smoke tumor promoters, catechol and hydroquinone, induce oxidative regulation of protein kinase C and influence invasion and metastasis of lung carcinoma cells.

Gopalakrishna

Chen

Gundimeda

1994

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

101

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Cigarette smoke polyphenolic agents (catechol and hydroquinone) that generate oxidants have been shown to be tumor promoters. Furthermore, oxidants can influence protein kinase C (PKC)-mediated signal transduction. Since terpenoid tumor promoters, phorbol esters, increase invasion and metastasis by activating PKC, we have determined whether polyphenolic agents present in the cigarette smoke condensate (CSC) could also influence these events. Hydroquinone (50 atM), catechol (500 pM), or CSC (50 jpg/ml) induced an initial cytosol-to-membrane translocation of PKC in LL/2 lung carcinoma cells, followed by a later down-regulation of the enzyme. LL/2 cells treated with these CSC-related agents for a limited time (45 min) and exhibiting high membrane-assodated PKC activity, when iqjected into mice through the tail vein, produced an increase in metastatic nodules in the lungs after 20 days. However, cells treated with CSC-related agents for a prolonged period did not exhibit an increase in metastasis. Agents that decrease the rate of production of reactive oxygen species, such as catalase either alone or in combination with superoxide dismutase, and a cellpermeable iron-chelator, o-phenanthroline, inhibited CSCmediated membrane association of PKC and metastasis. Prior treatment of CSC with tyrosinase to modify polyphenols resulted in a partial loss of CSC stimulation of meta . Furthermore, a cell-permeable Ca2+ chelator and diverse PKC inhibitors, such as calphostin C, hypericin, chelerythrine, and bisindolylmaleimide, inhhbited CSC-enhanced metastasis. CSC increased in vitro tumor cell adhesion to endothellal monolayers and to reconstituted basement membrane (Matrgel) and also enhanced the invasion through Matrigel coated on the polycarbonate filters in Transwells. Al these CSC effects were found to be temporary and were blocked by the above mentioned antioxidant systems and PKC inhibitors. Thus, these results suggest that the oxidants generated by autooxidation of polyphenolic agents present in tobacco smoke increase tumor cell invasion and metastasis, at least in part by activation of Ca2+/PKC signal transduction. Conceivably, cigarette smoke constituents not only promote tumorigenesis but also may increase the spread of cancer in the body.Epidemiological studies have established a causal relationship between cigarette smoking and respiratory tract cancer (1). The most important group oftumor promoters in tobacco smoke is reported to be the catechols (2, 3). Tumor promoting hydroquinone (HQ) is also present in the cigarette smoke at a high concentration (1). Catechols from cigarette smoke are also reported to generate hydrogen peroxide and superoxide free radicals (4,5). Moreover, reactive oxygen species appear to play an important role in tumor promotion (6)(7)(8).Lung carcinoma metastasizes with a great frequency and often at an early stage while primary growth is still small and asymptomatic (9). Moreover, several clinical studies in humans presented an association between smoking and an increase in metast...

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Tobacco-borne siderophoric activity

Cited by 27 publications

References 18 publications

Mitochondrial DNA Damage in Iron Overload

Mitochondrial DNA Damage in Iron Overload

Induction and Modulation of Lung Tumors: Genomic and Transcriptional Alterations in Cigarette Smoke-exposed Mice

Tobacco smoke tumor promoters, catechol and hydroquinone, induce oxidative regulation of protein kinase C and influence invasion and metastasis of lung carcinoma cells.

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