8-hydroxy-2--deoxyguanosine and Precursor-Cell-Lymphoblastic-Leukemia-Lymphoma

Thioredoxin-1 (TXN) is a key element in the elimination of reactive oxygen species as well as activation of tumor suppressor genes and DNA repair enzymes. Several studies showed that TXN was over expressed in solid tumors and this was correlated to poorer prognosis. However, TXN expression has been insufficiently studied, particularly in newly diagnosed adult acute leukemia.. This study was designed to evaluate the gene expression of TXN in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) adult patients and to investigate its association with oxidative DNA damage. The expression of TXN was analyzed using quantitative reverse transcriptase-polymerase chain reaction while oxidative DNA damage was evaluated by measuring serum 8-hydroxy-2-deoxyguanosine (8-OHdG) by enzyme-linked immunosorbent assay and strand breaks by the comet assay.. We found that TXN was under expressed in both AML and ALL groups (P < 0.001 for both) as compared to the control group. Also TXN expression level was negatively correlated with serum 8-OHdG and tail moment in both AML (P = 0.042 and 0.047, respectively) and ALL (P < 0.001 and P = 0.02, respectively) while it showed no correlation with treatment outcome in either groups.. This study suggests that TXN expression is hindered in adult acute leukemia which augments oxidative DNA damage and hence mutagenesis.. This study provides a new insight into the pathogenesis of acute leukemia and suggests TXN as a new screening test for the risk for acute leukemia.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Aged; Deoxyguanosine; DNA Damage; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Oxidative Stress; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Thioredoxins; Treatment Outcome; Young Adult

The 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, not only is a widely used biomarker for the measurement of endogenous oxidative DNA damage, but might also be a risk factor for many diseases including cancer. Elevated level of urinary 8-OHdG has been detected in patients with various malignancies. In the present study, the level of urinary 8-OHdG was examined in 116 Chinese children with acute leukemia (94 acute lymphoid leukemia, ALL, 22 acute myeloid leukemia, AML), and its correlation with urinary metal elements was investigated. Our result showed that the level of urinary 8-OHdG in children with acute leukemia before treatment was significantly elevated compared with that in normal controls (11.92 +/- 15.42 vs. 4.03 +/- 4.70 ng/mg creatinine, P < 0.05). In particular, urinary 8-OHdG was higher in children with acute leukemia aged under 3 years (20.86 +/- 21.75 ng/mg creatinine) than in those aged 3-15 years (8.09 +/- 9.65 ng/mg creatinine), whereas no differences were shown in terms of gender, parental smoking and education, household income, place of residence, and use of paracetamol. In addition, urinary 8-OHdG levels were similar among different subtypes of acute lymphoid leukemia (ALL) patients. Furthermore, linear regression analysis revealed a significant correlation between urinary 8-OHdG and urinary Cr, but not Fe or As, in group aged <3 years compared with group aged 3-15 years (P = 0.041), indicating that the metal elements may be involved in increasing urinary 8-OHdG level in younger children with acute leukemia. Our results suggest that children with acute leukemia undergo an increased risk of oxidative DNA damage, which may be correlated with high level of Cr exposure in Chinese children with acute leukemia.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Asian People; Carcinogens; Child; Child, Preschool; China; Deoxyguanosine; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Infant, Newborn; Leukemia, Myeloid, Acute; Male; Metals; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors

The 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, not only is a widely used biomarker for the measurement of endogenous oxidative DNA damage but might also be a risk factor for many diseases including cancer. Metal exposure may play an important role in oxidative DNA damage among children. However, few studies on urinary 8-OHdG and metals have been conducted in children with acute leukemia. In the present study, urinary Ni and 8-OHdG were examined in 116 children with acute leukaemia (94 acute lymphoid leukaemia [ALL] and 22 acute myeloid leukaemia [AML]) and 51 healthy child controls. Our result showed that urinary Ni in acute leukaemia patients (ALL: 68.40 +/- 133.98, AML: 41.48 +/- 76.31 ng/mg creatinine) was significantly higher than that in controls (62.47 +/- 124.90 vs 17.63 +/- 46.17 ng/mg creatinine, P < 0.05). Similarly, the pretherapy level of urinary 8-OHdG in patients (ALL: 11.83 +/- 16.23, AML: 12.36 +/- 11.36 ng/mg creatinine) was significantly elevated compared with controls (11.92 +/- 15.42 vs 4.03 +/- 4.70 ng/mg creatinine, P < 0.05). Moreover, urinary 8-OHdG and urinary Ni showed a weak but significant association with increased risk of childhood leukaemia. The present study suggests that Ni may be an etiologic factor for childhood acute leukaemia by oxidative DNA damage.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Analysis of Variance; Biomarkers; Child; Child, Preschool; China; Deoxyguanosine; DNA Damage; Female; Humans; Infant; Leukemia, Myeloid, Acute; Logistic Models; Male; Metals, Heavy; Metals, Light; Nickel; Oxidative Stress; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Children undergoing treatment for acute lymphoblastic leukemia (ALL) receive combination chemotherapy and many of the components are associated with free radical production.. Among 103 children newly diagnosed with ALL, plasma concentrations of antioxidants, total antioxidant capacity (ORAC), and DNA oxidized base 8-oxodeoxyguanosine (8-oxo-dG) were analyzed at baseline and 3 and 6 months after diagnosis.. Plasma vitamin A, antioxidants, 8-oxo-dG, and ORAC changed from diagnosis through the first 6 months of ALL therapy. In patients with higher plasma concentrations of vitamin A, E, total carotenoids, ORAC, and 8-oxo-dG there was a beneficial association with fewer dose reductions, fewer infections, improved quality of life, less delay in chemotherapy treatment schedule, reduced toxicity, and fewer days spent in the hospital. There were also adverse relationships demonstrated.. Among children with ALL, antioxidant levels and oxidative stress appear to be associated with duration and complications of treatment.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adolescent; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Child; Child, Preschool; Deoxyguanosine; Female; Humans; Infant; Male; Oxidative Stress; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prospective Studies; Regression Analysis; Treatment Outcome; United States