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

[b]Introduction and objective[/b]. 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. [b]Materials and methods[/b]. We compared the frequency of single nucleotide polymorphisms in genes coding for matrix proteinases ([i]MMP1, MMP2, MMP3, MMP9, MMP12[/i]) as well as tissue inhibitor of metalloproteinases ([i]TIMP1[/i]) in two groups of subjects: COPD patients (54 subjects) and COPD patients diagnosed for lung cancer occurrence (53 subjects).The levels of the respective proteins in blood serum were also analyzed. [b]Results[/b]. The frequencies of 2 genotypes, [i]MMP3[/i] rs3025058 and MMP3 rs678815, were significantly different between the studied groups. In both cases, more heterozygotes and less homozygotes (both types) were observed in the COPD group than in the COPD + cancer group. A significantly higher TIMP1 level in blood serum was observed in the COPD + cancer group than in the COPD group. There were no statistically significant differences in[i] MMPs[/i] blood levels between the studied groups. In addition, no genotype-associated differences in [i]TIMP1[/i] or[i] MMPs[/i] blood levels were observed. [b]Conclusions[/b]. Homozygocity for [i]MMP3[/i] rs3025058 and rs678815 polymorphisms is a potential marker of enhanced susceptibility to lung cancer development among COPD subjects

The rapid interphase chromosome assay (RICA) implementation: comparison with other PCC methods

A report is presented on the advantages of the rapid interphase chromosome assay (RICA) and the difficulties that may be met while implementing this method for application in biological dosimetry. The RICA test can be applied on unstimulated human lymphocytes; this is an advantage in comparison with the dicentric chromosomes or micronucleus tests. In the former two tests, stimulated lymphocytes are examined and hence, 48 h more are needed to obtain cells traversing the cell cycle. Due to the use of unstimulated nondividing cells, higher numbers of cells are available for RICA analysis than for dicentric chromosomes or micronuclei tests. Moreover, the method can be applied after exposure to ionizing radiation doses in excess of 5 Gy. Such doses cause a significant cell cycle delay or result in the loss of G2 phase and mitotic cells because of apoptosis. Therefore, the traditional biodosimetry based on the evaluation of the incidence of damage to chromosomes is very difficult to carry out. This is due to the lack of an adequate number of mitotic cells for analysis. RICA is free of this disadvantage. An automatic microscope can be used to retrieve cell images; automatic image analysis can also be used

No evidence of the long-term in vitro toxicity of Aeroxide P25 TiO2 nanoparticles in three mammalian cell lines despite the initial reduction of cellular mitochondrial activity

We studied the effects of Aeroxide P25 titanium dioxide nanoparticles (TiO2 NPs) with a diameter of 21 nm on induction of DNA damage and long-term survival of three human cell lines: hepatocellular liver carcinoma HepG2, colorectal adenocarcinoma HT29 and lung carcinoma A549. The endpoints examined were DNA breakage estimated by the comet assay and oxidative base damage recognized by formamide-pyrimidine glycosylase (FPG) estimated with the FPG+ comet assay, frequencies of histone γH2AX foci and micronuclei, apoptosis, cell metabolic activity measured by mitochondrial activity (MTT) assay and long-term survival measured by colony-forming ability. Each cell line had a different pattern of DNA breakage and base damage vs. nanoparticle (NP) concentration and treatment time. There was no increase in the frequencies of histone γH2AX foci and micronuclei as compared to those in the untreated cells. In parallel with these results, no induction of apoptosis has been found in none of the cell lines tested. The reported experiments provided no evidence of the long-term in vitro toxicity of Aeroxide P25 TiO2 NPs, despite a slight decrease in mitochondrial activity and cell survival during the first 72 h