Oxidative stress levels are correlated with P15 and P16 gene promoter methylation in myelodysplastic syndrome patients

被引：26

作者：

Goncalves, Ana Cristina ^{[1
,2
]}

Cortesao, Emilia ^{[1
,3
]}

Oliveiros, Barbara ^{[4
]}

Alves, Vera ^{[5
]}

Espadana, Ana Isabel ^{[3
]}

Rito, Luis ^{[1
,3
]}

Magalhaes, Emilia ^{[3
]}

Pereira, Sonia ^{[6
]}

Pereira, Amelia ^{[6
]}

Nascimento Costa, Jose Manuel ^{[7
,8
]}

Mota-Vieira, Luisa ^{[9
,10
,11
]}

Sarmento-Ribeiro, Ana Bela ^{[1
,2
,3
]}

机构：

[1] Univ Coimbra FMUC, Univ Clin Hematol, Ctr Invest Environm Genet & Oncobiol CIMAGO, Appl Mol Biol,Fac Med, P-3000548 Coimbra, Portugal

[2] Ctr Neurosci & Cell Biol CNC, Coimbra, Portugal

[3] CHUC, Dept Clin Hematol, Coimbra, Portugal

[4] Univ Coimbra FMUC, Lab Biostat & Med Informat, Fac Med, Coimbra, Portugal

[5] Univ Coimbra FMUC, Immunol, Fac Med, Coimbra, Portugal

[6] Hosp Dist Figueira da Foz, Dept Med, Figueira Da Foz, Portugal

[7] CHUC, Dept Oncol, Coimbra, Portugal

[8] Univ Coimbra FMUC, Univ Clin Oncol, Fac Med, Coimbra, Portugal

[9] Hosp Divino Espirito Santo Ponta Delgada EPE, Mol Genet & Pathol Unit, Sao Miguel Isl, Azores, Portugal

[10] Inst Gulbenkian Ciencias, Azores Genet Res Grp, Oeiras, Portugal

[11] Univ Lisbon, Biosyst & Integrat Sci Inst BioISI, Fac Sci, Lisbon, Portugal

来源：

CLINICAL AND EXPERIMENTAL MEDICINE | 2016年 / 16卷 / 03期

关键词：

Oxidative stress; DNA methylation; Myelodysplasia; Tumor suppressor genes; DNA-DAMAGE; EPIGENETIC CHANGES; SERUM FERRITIN; IRON OVERLOAD; BLOOD-CELLS; HYPERMETHYLATION; CANCER; APOPTOSIS; DIAGNOSIS; FREQUENT;

D O I：

10.1007/s10238-015-0357-2

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Oxidative stress and abnormal DNA methylation have been implicated in some types of cancer, namely in myelodysplastic syndromes (MDS). Since both mechanisms are observed in MDS patients, we analyzed the correlation of intracellular levels of peroxides, superoxide anion, and glutathione (GSH), as well as ratios of peroxides/GSH and superoxide/GSH, with the methylation status of P15 and P16 gene promoters in bone marrow leukocytes from MDS patients. Compared to controls, these patients had lower GSH content, higher peroxide levels, peroxides/GSH and superoxide/GSH ratios, as well as higher methylation frequency of P15 and P16 gene promoters. Moreover, patients with methylated P15 gene had higher oxidative stress levels than patients without methylation (peroxides: 460 +/- A 42 MIF vs 229 +/- A 25 MIF, p = 0.001; superoxide: 383 +/- A 48 MIF vs 243 +/- A 17 MIF, p = 0.022; peroxides/GSH: 2.50 +/- A 0.08 vs 1.04 +/- A 0.34, p < 0.001; superoxide/GSH: 1.76 +/- A 0.21 vs 1.31 +/- A 0.10, p = 0.007). Patients with methylated P16 and at least one methylated gene had higher peroxide levels as well as peroxides/GSH ratio than patients without methylation. Interestingly, oxidative stress levels allow the discrimination of patients without methylation from ones with methylated P15, methylated P16, or at least one methylated (P15 or P16) promoter. Taken together, these findings support the hypothesis that oxidative stress is correlated with P15 and P16 hypermethylation.

引用

页码：333 / 343

页数：11

共 52 条

[1] Myelodysplastic syndromes [J].