Oxidative DNA damage of peripheral blood polymorphonuclear leukocytes, selectively induced by chronic arsenic exposure, is associated with extent of arsenic-related skin lesions.

There is increasing evidence that oxidative stress is an important risk factor for arsenic-related diseases. Peripheral blood leukocytes constitute an important defense against microorganisms or pathogens, while the research on the impact of chronic arsenic exposure on peripheral blood leukocytes is much more limited, especially at low level arsenic exposure. The purpose of the present study was to explore whether chronic arsenic exposure affects oxidative stress of peripheral blood leukocytes and possible linkages between oxidative stress and arsenic-induced skin lesions. 75 male inhabitants recruited from an As-endemic region of China were investigated in the present study. The classification of arsenicosis was based on the degree of skin lesions. Arsenic levels were measured in drinking water and urine by Atomic Fluorescence Spectroscopy. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was tested by Enzyme-Linked Immunosorbent Assay. 8-OHdG of peripheral blood leukocytes was evaluated using immunocytochemical staining. 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs), but not in monocytes (MNs). The 8-OHdG staining of PMN cytoplasm was observed in all investigated populations, while the 8-OHdG staining of PMN nuclei was frequently found along with the elevated amounts of cell debris in individuals with skin lesion. Urinary arsenic levels were increased in the severe skin lesion group compared with the normal group. No relationship was observed between drinking water arsenic or urine 8-OHdG and the degree of skin lesions. These findings indicated that the target and persistent oxidative stress in peripheral blood PMNs may be employed as a sensitive biomarker directly to assess adverse health effects caused by chronic exposure to lower levels of arsenic.

[Effect of prostaglandin E2 and the tumor necrosis factor-alpha on second messenger of lung fibroblast].

OBJECTIVE: To Study the effect of prostaglandin E(2) (PGE(2)) combined with tumor necrosis factor-alpha (TNF-alpha) on the second messenger of mouse lung fibroblast in order to research new target point for cytokine to treatment of pneumoconiosis. METHODS: The lung fibroblasts of breed mouse were primarily cultured. 10 ng/ml TNF-alpha and 10 ng/ml TNF-alpha combined with PGE(2) of different doses were added to culture medium of fibroblasts. The gamma value and CPM value were respectively measured for second messenger of cAMP, cGMP and IP(3) of fibroblast by immune-radio assay at different observation time. RESULTS: When treated with 10 ng/ml TNF-alpha + 1,000 pg/ml PGE(2) at 120 s time points, the CPM value of IP(3) of fibroblast was the maximal value [(76.33 +/- 7.10) CPM]; when cAMP/cGMP ratio declined to 4.29 at 24 h time point, the effect of fibroblast proliferation was the strongest; when 10 ng/ml TNF-alpha + 500 pg/ml PGE(2), and 2 000 pg/ml PGE(2), the CPM value of IP(3) of fibroblast were 27.00 +/- 3.00 and 61.00 +/- 2.65 respectively at 120 s time point, cAMP/cGMP value were 3.50 and 9.83 respectively at 24 h, the effect on fibroblast proliferation were obviously lower. CONCLUSION: Certain dose of PGE(2) could raise the ratio of cAMP/cGMP of fibroblast, and antagonize the proliferation effect of TNF-alpha on fibroblast.