Biomarkers for chronic arsenic poisoning

Faye Fang Liu (2004). Biomarkers for chronic arsenic poisoning MPhil Thesis, School of Medicine, The University of Queensland.

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Author Faye Fang Liu
Thesis Title Biomarkers for chronic arsenic poisoning
School, Centre or Institute School of Medicine
Institution The University of Queensland
Publication date 2004
Thesis type MPhil Thesis
Supervisor A/Prof Jack Ng
A/Prof Barry Chiswell
Prof Michael R. Moore
Total pages 205
Collection year 2005
Language eng
Subjects L
321299 Public Health and Health Services not elsewhere classified
730210 Environmental health
Formatted abstract

It is well known that arsenic is toxic to both humans and animals, and that inorganic arsenic compounds are proven human carcinogens. Arsenic contamination of drinking water is a global health issue, especially in the South East Asian countries. Dzungaria in Xinjiang, China, with a population of 100,000, was the first identified arsenic endemic area in mainland China with a sustained arsenic concentration in underground water of approximately 50 µg/L, whereas in Kuitun arsenic levels in the underground water may reach a concentration as high as 850 µg/L. Although a water intervention program was implemented and completed in 1984, arsenicosis still occurs in the region at present.  


We studied biomarkers, including total urinary arsenic, porphyrins and malondiadehyde in the arsenic endemic area in Xinjiang. The results show that urinary arsenic levels within the endemic region vary from 4.19 to 943.76 µg/g creatinine, with an average of 117.03 ± 8.28 µg/g creatinine (n = 168), which was significantly higher than in the control area (73.61± 3.21 µg/g creatinine; n = 152). Although no significant difference was found between villagers overall from the endemic area and control region in the levels of urinary porphyrins and malondialdehyde (MDA), both porphyrins and MDA levels were significantly higher in those villagers of endemic region with urinary arsenic levels higher than 150 µg/g creatinine, the recommended occupational exposure limit set by Worksafe Australia (Marshall, 2002). 


In this study, it was found that 51 out of 178 people from the arsenic endemic area displays symptoms of arsenicosis whilst arsenicosis is absent in the control region where a total of 175 people were surveyed. This clearly indicates that not all people in the arsenic endemic region of Chepaizi area in Dzungaria were drinking arsenic safe water only and that arsenicosis is still a serious problem in Xinjiang. Although porphyrins and malondialdehyde are sensitive biomarkers for arsenicosis for villagers with urinary arsenic levels higher that 150 µg/g creatinine, they are not sensitive for villagers with lower urinary arsenic levels. With a population that has a large variation in drinking habits, further study is needed to quantify the health outcome for these individuals although the water intervention program has been in place for over 16 years. 


Another part of this project involved a preliminary immunohistochemical staining trial on the first animal model of arsenic carcinogenicity that was successfully developed in the National Research Centre for Environmental Toxicology by Ng et al. (1999b) in 1998. In this model, groups of 90 C57BL/6J and 140 virgin female MT knockout mice were fed with drinking water containing sodium arsenate (500µgAs/L ad libitum) for 26 months. Over this period, various organ systems of the exposed mice developed tumours. Preliminary findings indicate that 37/90 (41.1%) C57B1/6J and 37/140 (26.4%) MT'test mice developed one or more tumours (Ng et al., 2001; 1999b; 1998a). On a separate PhD project, 25 DNA samples from 24 tumour-bearing mice from the arsenic-treated group and 4 from the control group were screened for mutations in exons 5 and 7 of the p53 gene (Wang, 2003). In this study 20 formalin fixed, paraffin embedded tissue blocks from mice with known mutations were selected for immunohistochemical staining. In the initial trial, positive stains were indeed observed on some tissue sections. However, background staining on other tissues such as kidney is high, possibly related to a number of factors such as tissue fixation time, antigen retrieval (AR) buffer type especially pH, heating method and heating time on heat retrieval. Nevertheless, this initial trial does shed some light on the possibility to optimize AR conditions to compensate prolonged fixation time. Further testing is required to develop this technique into routine practice; this is beyond the scope of this MPhil project.  

Keyword Biochemical markers
Arsenic -- Toxicology
Arsenic -- Health aspects

Document type: Thesis
Collection: UQ Theses (RHD) - UQ staff and students only
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Created: Fri, 24 Aug 2007, 18:49:35 EST