Effect of genetic polymorphisms of MnSOD and MPO on the relationship between PAH exposure and oxidative DNA damage

Urinary hippuric acid (HA) has been widely used as a biological marker of occupational exposure to toluene, although it is no longer valid for low levels of toluene exposure. Toluene exposure is known to induce oxidative DNA damage and the metabolism is affected by genetic polymorphisms of some metabolizing enzymes. Therefore, genetic polymorphisms of these metabolizing enzymes must be considered in the evaluation of oxidative stress caused by toluene exposure. We evaluated the relationship between urinary 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and urinary HA in individuals without occupational exposure to toluene and characterized the possible roles of GSTM1, GSTT1, and aldehyde dehydrogenase 2 (ALDH2) genotypes in the relationships between these markers. In this study, we enrolled 92 healthy Koreans. Urinary HA and 8-OHdG levels were measured and the correlations between them were statistically tested according to the GSTM1, GSTT1, and ALDH2 genotypes. HA did not significantly correlate with urinary 8-OHdG in overall subjects. However, the correlation between them showed a statistical significance in individuals with GSTM1-null, GSTT1-null, and ALDH2 *2/*2 genotypes (r = 0.766, p < 0.01). This study shows that the relationship between urinary HA and 8-OHdG concentration is modified by genetic polymorphisms of some metabolizing enzymes such as GSTM1, GSTT1, and ALDH2.

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A multibiomarker approach to evaluate the effect of polyaromatic hydrocarbon exposure on oxidative and genotoxic damage in tandoor workers

Toxicology and Industrial Health ◽

10.1177/0748233719862728 ◽

2019 ◽

Vol 35 (7) ◽

pp. 486-496 ◽

Cited By ~ 1

Author(s):

Kanika Miglani ◽

Sunil Kumar ◽

Anita Yadav ◽

Neeraj Aggarwal ◽

Imteyaz Ahmad ◽

...

Keyword(s):

Dna Damage ◽

Oxidative Dna Damage ◽

Polyaromatic Hydrocarbons ◽

Multivariate Regression Analysis ◽

Work Conditions ◽

Control Population ◽

Work Exposure ◽

Genotoxic Damage ◽

Mda Content ◽

The Relationship

We conducted a cohort study of tandoor workers to evaluate the relationship between the biomarkers of oxidative and genotoxic damage and exposure to polyaromatic hydrocarbons. A series of oxidative and genotoxic damage biomarkers, including urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG), malondialdehyde (MDA) content, and tail moment (TM) by comet assay, was studied. A total of 76 tandoor workers and 79 demographically matched healthy individuals as controls were included. Our results showed that the tandoor workers had significantly higher urinary levels of 1-hydroxypyrene, urinary 8-OHdG, MDA content, and TM compared with the control population. The concentration of all these biomarkers increased with age in the control population as well as tandoor workers. In tandoor workers, significant variation in MDA, 8-oxodG (8-oxo-2′-deoxyguanosine) and TM concentration was detected between smokers (5.08 ± 1.72 nmol/mL, 16.01 ± 4.94 ng/mg creatinine, and 5.87 ± 0.98 µm, respectively) and nonsmokers (3.84 ± 0.98 nmol/mL, 13.74 ± 3.60 ng/mg creatinine, and 5.32 ± 0.69 µm, respectively). A similar pattern was obtained for the control population. We did not obtain significant variations for alcoholics and tobacco chewers. A significant increase in all these three biomarkers was observed with the increase in the period of work exposure in tandoor workers. Multivariate regression analysis also revealed that urinary 8-oxodG, MDA, and TM were statistically significantly related to age and period of work exposure. Overall, the present study showed that the exposure to wood smoke in tandoor workers under occupational conditions led to increased DNA damage because of oxidative stress and genotoxicity. These biomarkers, therefore, are good indices to assess oxidative DNA damage in these workers exposed to occupational genotoxicants. It is also necessary to make preventive changes in work conditions and lifestyle, which will help these occupational workers to lead a healthy life.

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Oxidative DNA damage and influence of genetic polymorphisms among urban and rural schoolchildren exposed to benzene

Chemico-Biological Interactions ◽

10.1016/j.cbi.2008.01.005 ◽

2008 ◽

Vol 172 (3) ◽

pp. 185-194 ◽

Cited By ~ 51

Author(s):

Nantaporn Buthbumrung ◽

Chulabhorn Mahidol ◽

Panida Navasumrit ◽

Jeerawan Promvijit ◽

Potchanee Hunsonti ◽

...

Keyword(s):

Dna Damage ◽

Genetic Polymorphisms ◽

Oxidative Dna Damage

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Methods to detect DNA damage by free radicals: relation to exercise

Proceedings of The Nutrition Society ◽

10.1017/s0029665199001329 ◽

1999 ◽

Vol 58 (4) ◽

pp. 1007-1014 ◽

Cited By ~ 42

Author(s):

Henrik E. Poulsen ◽

Allan Weimann ◽

Steffen Loft

Keyword(s):

Mass Spectrometry ◽

Dna Damage ◽

Oxidative Dna Damage ◽

Dna Oxidation ◽

Dna Bases ◽

Strenuous Exercise ◽

Local Concentration ◽

Long Duration ◽

Liquid Chromatography Tandem Mass ◽

The Relationship

Epidemiological investigations repeatedly show decreased morbidity from regular exercise compared with sedentary life. A large number of investigations have demonstrated increased oxidation of important cellular macromolecules, whereas other investigators have found no effects or even signs of lowering of oxidation of macromolecules. In particular, extreme and long-duration strenuous exercise appears to lead to deleterious oxidation of cellular macromolecules. The oxidation of DNA is important because the oxidative modifications of DNA bases, particularly the 8-hydroxylation of guanine, are mutagenic and have been implicated in a variety of diseases such as ageing and cancer. The methodologies for further investigation of the relationship between DNA oxidation and exercise are available. The preferred methods rely on HPLC or GC-mass spectrometry; whereas the theoretically-attractive liquid chromatography- tandem mass spectrometry is being developed. Caution should be taken to avoid artifacts because of the six orders of magnitude of difference between oxidized and non-oxidized DNA bases in tissues. The methods can be used to estimate tissue levels, i.e. a local concentration of oxidized DNA, or to estimate the rate of body DNA oxidation by the urinary output of repair products, the latter being a method that is independent of repair. During exercise there appears to be a shifting of dietary-dependent antioxidant, e.g. vitamin C and vitamin E, from muscle to plasma, and an increased oxidation in plasma of these antioxidants. Supplementation trials with antioxidants have not been able to increase exercise performance; however, optimum nutrition with antioxidants and possibly supplementation, could be important in the prevention of diseases in the long term. The pattern from these observations appears to be quite consistent; immediately after exercise, regardless of how intense, there do not appear to be any signs of oxidative damage to DNA. Acute or prolonged moderate exercise does not produce signs of oxidative DNA damage and might even be associated with lowering of the levels of oxidation of tissue DNA; however, after long-duration and intense exercise an increase in oxidative DNA modifications is apparent. We suggest as a hypothesis that the relationship between exercise and health is U-shaped. This hypothesis needs to be tested in detail in order to establish the maximum beneficial exercise level with regard to oxidative DNA modification, and also the level that could be deleterious and might even increase the risk for cancer and other diseases.

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