R. Maddalena

Arsenicosis status and urinary malondialdehyde (MDA) in people exposed to arsenic contaminated-coal in China

The current arsenic exposure condition, arsenicosis prevalence, urinary arsenic and MDA (malondialdehyde) concentrations in people were studied. The study area, a village in Xing Ren County in Guizhou Province, PR China, is a coal-borne arsenicosis endemic area that was identified several decades ago. The residents in Xing Ren have been using coal containing high arsenic levels all their life. Urinary arsenic levels of villagers were 192.2+/-22 microg/g creatinine (n=113) in the coal-borne endemic area (Xing Ren county) and were significantly higher than 63.6+/-5.9 microg/g creatinine (n=30) in a neighbouring control site (a village in Xing Yi county). The urinary MDA concentrations of villagers from the endemic area were also significantly higher compared to those of the control area. There was a strong correlation between age and urinary arsenic and MDA concentrations in the endemic area of Xing Ren; urinary arsenic and MDA levels decreased with age. Fifty out of 113 (44.3%) villagers in the endemic area had arsenicosis symptoms and the prevalence in villagers older than 40 y was 100% in male (92.2% overall). Urinary MDA concentration was significantly higher in people with arsenicosis symptoms in the endemic areas. Oxidative stress (urinary MDA concentration) was strongly related to arsenic exposure but not to the age and smoking habit. Higher urinary arsenic and MDA levels in younger villagers from the endemic area suggest that they are having a higher exposure to coal-borne emitted arsenic because they spend more time indoor. There is an urgent need to develop proper intervention methods in the Guizhou endemic areas in order to reduce the risk to the local communities who are still using arsenic contaminated-coal.

Use of urinary porphyrin profile as an early warning biomarker for Monomethylarsonous Acid (MMAIII) exposure

Although it is well known that arsenic is toxic and that Arsenic is carcinogenic, the mechanism underlying this carcinogenesis is unknown. Our laboratories have established a model that produces multi-organ tumours in mice following extended exposure to arsenic in drinking water. Until recently the metabolism of arsenic was thought to be a detoxification process. Recent studies have shown that Monomethylarsonous acid (MMA(III)) is the toxic intermediate of arsenic metabolism. It is a more potent cytotoxin and genotoxin than As-III and As-V, and is believed to be the proximal carcinogen. Exposure to arsenic is known to affect the activity of the enzymes of haem biosynthesis. We evaluated the use of urinary porphyrin profiles as an early warning biomarker for arsenic carcinogenicity. Young female mice were given drinking water containing arsenic as MMA(III) ad libitum. 24h urine samples were collected at various time intervals for up to 48 weeks for urinary arsenic accumulation by HPLC-ICPMS and urinary porphyrin measurement by HPLC. Dimethylarsinic acid (DMA(V)) was the major metabolite excreted and it showed significant dose-dependent increase at each time point and exposure dependent increase over 48 weeks. Porphyrin levels appeared to be age dependent. The results indicate that the urinary porphyrin concentration has the potential for use as an early warning indicator of chronic arsenic exposure prior to the onset of arsenic carcinogenesis.

Porphyrins and malondialdehyde as early biomarkers in individuals exposed to arsenic-contaminated coal in Guizhou, PR China: Isee-687

Introduction Coal is widely used in PR China. Unfortunately, coal from some areas in Guizhou Province contains elevated levels of arsenic. This has caused arsenicosis in individuals who use arsenic-contaminated coal for the purposes of cooking, heating and drying food. Aims Porphyrins are produced during heme biosynthetic pathways. Malondialdehyde (MDA) has been used to evaluate lipid peroxidation and DNA damage caused by exogenous free radicals or endogenous reactive oxygen species (ROS). This study aims to measure porphyrins and MDA and investigate their potential as early biomarkers of chronic arsenic poisoning. Methods We used HPLC to analyse porphyrin excretion profiles in urine samples from 113 people who live in Xing Ren of Guizhou Province, a coal-borne arsenicosis endemic area and from 30 control samples from Xing Yi where arsenicosis is not prevalent. We analysed urinary MDA by GC-MS in 119 and 30 urine samples obtained from the endemic and control sites respectively. Results Urinary porphyrins and MDA were higher in all arsenic exposed individuals than those of controls. Correlation between the urinary arsenic levels and porphyrin concentrations demonstrated the effect of arsenic on heme biosynthesis resulting in increased porphyrin excretion. Greater increases of urinary arsenic and porphyrin profiles in women, children and older age groups who spend much of their time indoors suggest that they might be at a higher risk. MDA concentrations were significantly higher in young age and female exposed groups than the controls. This confirmed the existence of lipid peroxidation and oxidative stress induced by chronic arsenic exposure. Conclusions Porphyrins and MDA are potential early biomarkers of arsenicosis. Elevated levels of porphyrins and MDA could lead to adverse health effects in chronically arsenic-exposed individuals associated with both non-cancer and cancer end-points.