Carcinogenesis-related changes in iron metabolism in chronic obstructive pulmonary disease subjects with lung cancer.

Chronic obstructive pulmonary disease (COPD) is often accompanied by lung cancer. In our previous work, it was observed that matrix metalloproteinase-3 and haptoglobin () polymorphisms were potential markers of enhanced susceptibility to lung cancer development among male COPD subjects. Here, results are reported on blood serum levels of several proteins involved in iron metabolism, inflammation and the oxidative stress response compared between the same groups of subjects.

Matrix metalloproteinase 3 polymorphisms as a potential marker of enhanced susceptibility to lung cancer in chronic obstructive pulmonary disease subjects.

Introduction And Objective: Chronic obstructive pulmonary disease (COPD) is often accompanied by lung cancer. Among the genes that may play a role in the occurrence of COPD and lung cancer are those encoding the proteolytic enzymes, such as matrix metalloproteinases (MMPs) and their tissue inhibitors. The objective of this study was to find MMPs-associated markers useful in the identification of COPD subjects with increased susceptibility to developing lung cancer.

Silver nanoparticles -- allies or adversaries?

Nanoparticles (NP) are structures with at least one dimension of less than 100 nanometers (nm) and unique properties. Silver nanoparticles (AgNP), due to their bactericidal action, have found practical applications in medicine, cosmetics, textiles, electronics, and other fields. Nevertheless, their less advantageous properties which make AgNP potentially harmful to public health or the environment should also be taken into consideration.

Oxidative DNA damage corresponds to the long term survival of human cells treated with silver nanoparticles.

We examined the relation between DNA damage and the clonogenic potential of 3 human cell lines, HepG2, HT29 and A549, treated with bare 20 nm or 200 nm silver nanoparticles (AgNPs). The endpoints examined were the DNA breakage estimated by the comet assay, the oxidative base damage recognized by formamido-pyrimidine glycosylase (FPG) and estimated with the FPG+comet assay, and the frequencies of histone γH2AX foci and micronuclei. Each cell line studied had a different pattern of DNA breakage and base damage versus the NPs concentration and time of treatment.

Cu,Zn-superoxide dismutase deficiency in mice leads to organ-specific increase in oxidatively damaged DNA and NF-κB1 protein activity.

Earlier experimental studies have demonstrated that: i) Cu,Zn-superoxide dismutase deficiency leads to oxidative stress and carcinogenesis; ii) dysregulation of NF-κB pathway can mediate a wide variety of diseases, including cancer. Therefore, we decided, for the first time, to examine the level of oxidative DNA damage and the DNA binding activity of NF-κB proteins in SOD1 knockout, heterozygous and wild-type mice. Two kinds of biomarkers of oxidatively damaged DNA: urinary excretion of 8-oxodG and 8-oxoGua, and the level of oxidatively damaged DNA were analysed using HPLC-GC-MS and HPLC-EC.

Hepatic iron content corresponds with the susceptibility of lymphocytes to oxidative stress in neonatal pigs.

The pig is born with limited iron supplies. If not supplemented, piglets dramatically loose their body iron stores during the first few days of postnatal life. The aim of this study was to investigate the influence of hepatic iron content on susceptibility of blood cells to oxidative stress.

Inhibition of poly(ADP-ribose)polymerase does not affect the recombination events in CHO xrs6 and wild type cells.

Activation of poly (ADP-ribose) polymerase -1 (PARP-1) is an early DNA damage response event that, together with phosphorylation of p53, prompts various cellular functions important in the maintenance of the genome stability. In mammalian cells, DSB are repaired by nonhomologous end-joining (NHEJ) and by homologous recombination (HR). To investigate the role of PARP-1 in HR, CHO-K1 wild type and xrs-6 mutant cell line were transfected with pLrec plasmids which carry two nonfunctional copies of the beta-galactosidase (lacZ) gene in a tandem array.

Induction of iron regulatory protein 1 RNA-binding activity by nitric oxide is associated with a concomitant increase in the labile iron pool: implications for DNA damage.

Iron regulatory protein 1 (IRP1) is a bifunctional [4Fe-4S] protein that controls iron homeostasis. Switching off its function from an aconitase to an apo-IRP1 interacting with iron-responsive element-containing mRNAs depends on the reduced availability of iron in labile iron pool (LIP). Although the modulation of IRP1 by nitric oxide has been characterized, its impact on LIP remains unknown.

Down-regulation of iron regulatory protein 1 activities and expression in superoxide dismutase 1 knock-out mice is not associated with alterations in iron metabolism.

Iron and oxygen (O2) are intimately associated in many well characterized patho-physiological processes. These include oxidation of the [4Fe-4S] cluster of mitochondrial aconitase and inactivation of this Krebs cycle enzyme by the superoxide anion (O2*-), a product of the one-electron of reduction O2. In contrast to the apparent toxicity of this reaction, the biological consequences of O2*- -mediated inactivation of the cytosolic counterpart of mitochondrial aconitase, commonly known as iron regulatory protein 1 (IRP1), are not clear.

The level of 8-oxo-7,8-dihydro-2'-deoxyguanosine is positively correlated with the size of the labile iron pool in human lymphocytes.

It appears that the labile iron pool (LIP, low molecular weight iron) presence in cells can result in the production of reactive oxygen species (ROS). ROS may be responsible for the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in cellular DNA. In the present study we report on the relationship between LIP and the endogenous level of 8-oxodGuo in human lymphocytes.