Recent evidence suggests that active DNA demethylation involves base excision repair (BER) and nucleotide excision repair (NER) pathways. We hypothesized that the resulting excision products could be further excreted and present in urine. A highly specific and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was first developed for simultaneously measuring urinary 5-methylcytosine (5-meC) and 5-methyl-2'-deoxycytidine (5-medC). With the use of isotope internal standards and online solid-phase extraction (SPE), the detection limits of 5-meC and 5-medC were estimated to be 1.2 and 0.3 pg, respectively. This method was applied to measure urinary samples of 376 healthy males. Urinary samples were also measured for methylated and oxidized DNA lesions, namely, N7-methylguanine (N7-meG), N3-methyladenine (N3-meA), 8-oxo-7,8-dihydroguanine (8-oxoGua), and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), using reported online SPE LC-MS/MS methods. Results showed that mean urinary levels of 5-meC and 5-medC were 28.4 ± 14.3 and 7.04 ± 7.2 ng/mg creatinine, respectively, supporting the possible presence of DNA demethylation through BER and NER mechanisms. Urinary levels of 5-meC were significantly positively correlated with N7-meG, N3-meA, and 8-oxodG. Good correlations between 5-meC and methylated and oxidized DNA lesions may have implied the underlying linkage between genetic (DNA lesions) and epigenetic (DNA methylation) alterations derived from exogenous exposure and/or from endogenous cellular processes in human and require further investigation.
The purpose of this study was to examine the association of vitamin B6 status and plasma homocysteine with oxidative stress and antioxidant capacities in welders. Workers were divided into either the welding exposure group (n = 57) or the nonexposure controls (n = 42) based on whether they were employed as welders. There were no significant differences in vitamin B6 status and plasma homocysteine concentration between the welding exposure group and the nonexposure controls. The welding exposure group had significantly higher levels of oxidized low-density lipoprotein cholesterol and lower erythrocyte glutathione concentration and superoxide dismutase (SOD) activities when compared to nonexposure controls. Plasma pyridoxal 5′-phosphate concentration did not correlate with oxidative stress indicators or antioxidant capacities in either group. However, plasma homocysteine significantly correlated with total antioxidant capacity (TAC) (partial r
s = −0.34, P < 0.05) and erythrocyte SOD activities (partial r
s = 0.29, P < 0.05) after adjusting for potential confounders in the welding exposure group. In the welding exposure group, adequate vitamin B6 status was not associated with oxidative stress or antioxidant capacities. However, elevated plasma homocysteine seemed to be a major contributing factor to antioxidant capacities (TAC and erythrocyte SOD activities) in welders.
Increasing the number of poststerilization purge cycles is a simple approach to eliminating extremely high exposure during unloading. Improvements to ventilation, particularly in the aeration area and warehouse, were also effective in minimizing worker exposures. Use of effective respirator is recommended until the EO exposure levels, averaging 3.41 ppm after the controls, fall below the permissible exposure limit.
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