Relationship between 8-hydroxydeoxyguanosine levels in placental/umbilical cord blood and maternal/neonatal obstetric factors

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Abstract

Oxidative stress is associated with the development of various diseases including cancer, arteriosclerosis, diabetes mellitus, hypertension and metabolic syndrome. However, little is known about the involvement of 8-hydroxydeoxyguanosine (8-OHdG) during the perinatal period. At present, few studies have investigated the precise correlations between 8-OHdG levels in cord blood (CB) and the physical conditions of the mother and neonate. To clarify the involvement of 8-OHdG during the perinatal period, the relationships between CB 8-OHdG levels and maternal/neonatal characteristics in vaginal deliveries were determined. The 8-OHdG levels of CB units collected from singleton gestation vaginal deliveries were analyzed. The relationships between 8-OHdG levels and perinatal characteristics were analyzed. The 8-OHdG levels in CB ranged from 0.1 to 1.39 ng/ml (median, 0.37 ng/ml). The relationships between 8-OHdG levels and the perinatal data were analyzed. The 8-OHdG levels detected in the non-smoking group were significantly lower compared to those in the smoking group. However, no significant correlation was observed between 8-OHdG levels and other maternal/ neonatal factors, including umbilical artery acid/base and gas values. Maternal smoking increases the level of the oxidative DNA damage biomarker 8-OHdG in CB. Since oxidative stress may influence the long-term health outcomes of infants after birth, understanding maternal and fetus/neonate stress conditions at delivery may help improve the health of fetuses and infants.

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Most cited references 32

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Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG.

S Shibutani, M Takeshita, A P Grollman (1991)

Oxidative damage to DNA, reflected in the formation of 8-oxo-7-hydrodeoxyguanosine (8-oxodG), may be important in mutagenesis, carcinogenesis and the ageing process. Kuchino et al. studied DNA synthesis on oligodeoxynucleotide templates containing 8-oxodG, concluding that the modified base lacked base pairing specificity and directed misreading of pyrimidine residues neighbouring the lesion. Here we report different results, using an approach in which the several products of a DNA polymerase reaction can be measured. In contrast to the earlier report, we find that dCMP and dAMP are incorporated selectively opposite 8-oxodG with transient inhibition of chain extension occurring 3' to the modified base. The potentially mutagenic insertion of dAMP is targeted exclusively to the site of the lesion. The ratio of dCMP to dAMP incorporated varies, depending on the DNA polymerase involved. Chain extension from the dA.8-oxodG pair was efficiently catalysed by all polymerases tested.

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Increased serum levels of 8-hydroxy-2'-deoxyguanosine in clinical depression.

Michael Forlenza, Gregory E. Miller (2006)

We sought to understand the pathophysiological effects of depression by examining group differences in serum levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative damage. Our sample consisted of 169 participants. Eight-four of these participants met diagnostic criteria for clinical depression. The 85 participants in our comparison group were matched on age, gender, and ethnicity to the depressed group. 8-OHdG was measured by enzyme-linked immunosorbent assay. After adjusting for age, gender, race/ethnicity, years of education, daily smoking, average number of alcoholic drinks per week, average amount of physical activity per week, and body mass index, participants in the depressed group had significantly higher levels of oxidative DNA damage compared with participants in the control group. Pairwise comparisons showed that participants with major depression had significantly higher levels of 8-OHdG than control subjects and marginally higher levels of 8-OHdG compared with those with minor depression. Furthermore, participants with recurrent episodes of depression had more oxidative damage than participants with single episodes, who in turn had more damage than healthy control subjects. Finally, participants with recurrent episodes of major depression had more DNA damage than other depressed participants, who in turn had more damage than healthy control subjects. Our findings suggest that increased oxidative damage may represent a common pathophysiological mechanism, whereby depressed individuals become vulnerable to comorbid medical illness.

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Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender and body mass index.

S Loft, M Ewertz, K. Overvad … (1992)

Oxidative DNA damage may be implicated in ageing, carcinogenesis and other degenerative diseases. Oxidative DNA damage can be assessed in humans in vivo from the urinary excretion of the DNA-repair product 8-hydroxydeoxyguanosine (8OHdG). We investigated factors influencing the excretion of 8OHdG in 24 h urine from 83 randomly selected healthy subjects (52 women) aged 40-64 years. For 2 weeks prior to urine collection the subjects kept a weighed diet record. 8OHdG was quantified by an automatic three-dimensional HPLC analysis with electrochemical detection. The 8OHdG excretion was 252 +/- 103 (mean +/- SD) pmol kg body weight/24 h with a range from 78 to 527. Multiple regression analysis identified three factors, smoking, body mass index (BMI) and gender, as significant predictors of the 8OHdG excretion. In 30 smokers the 8OHdG excretion was 320 +/- 99 pmol/kg/24 h opposed to 213 +/- 84 pmol/kg/24 h in 53 non-smokers. According to multiple regression analysis smokers excreted 50% (31-69%; 95% confidence interval) more 8OHdG than non-smokers. In 52 women the 8OHdG excretion was 240 +/- 106 pmol/kg/24 h opposed to 271 +/- 96 pmol/kg/24 h in 31 men. According to the multiple regression analysis men excreted 29% (10-48%) more 8OHdG than women. According to multiple regression analysis the 8OHdG excretion decreased with 4% (2-6%) per increment in BMI measured in kg/m2. The dietary distribution of energy demonstrated no important predictive value with respect to 8OHdG excretion. The intake of the antioxidant vitamins C and E and of vitamin A equivalents, including beta-carotene, was not associated with 8OHdG excretion. The results suggest that smoking increases oxidative DNA damage by approximately 50%. This effect implies potential serious health effects adding to the other well-known health hazards of smoking. The higher 8OHdG excretion in men and lean subjects may be related to a higher rate of metabolism with increased availability of reactive oxygen species. The apparent 7-fold individual variation in oxidative DNA damage carries implications regarding the rate of ageing and the risk of cancer and other degenerative diseases. The excretion of 8OHdG into urine offers a valuable tool for testing such hypotheses in humans.

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Author and article information

Journal

Journal ID (nlm-ta): Exp Ther Med

Journal ID (iso-abbrev): Exp Ther Med

Journal ID (publisher-id): ETM

Title: Experimental and Therapeutic Medicine

Publisher: D.A. Spandidos

ISSN (Print): 1792-0981

ISSN (Electronic): 1792-1015

Publication date (Print): September 2012

Publication date (Electronic): 20 June 2012

Volume: 4

Issue: 3

Pages: 387-390

Affiliations

[1 ]Departments of Disability and Health and

[2 ]Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, Hirosaki 036-8564;

[3 ]Department of Obstetrics and Gynecology, Hirosaki National Hospital, Hirosaki 036-8545, Japan

Author notes

Correspondence to: Professor Ikuo Kashiwakura, Department of Radiological Life Sciences, Hirosaki University Graduate School of Health Sciences, 66-1 Hon-cho, Hirosaki 036-8564, Japan, E-mail: ikashi@ 123456cc.hirosaki-u.ac.jp

Article

Publisher ID: etm-04-03-0387

DOI: 10.3892/etm.2012.617

PMC ID: 3503545

PubMed ID: 23181104

SO-VID: 0006a79c-b360-4637-b8d9-793b74224b09

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This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

Relationship between 8-hydroxydeoxyguanosine levels in placental/umbilical cord blood and maternal/neonatal obstetric factors

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Most cited references 32

Insertion of specific bases during DNA synthesis past the oxidation-damaged base 8-oxodG.

Increased serum levels of 8-hydroxy-2'-deoxyguanosine in clinical depression.

Oxidative DNA damage estimated by 8-hydroxydeoxyguanosine excretion in humans: influence of smoking, gender and body mass index.

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