Biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in Taiwan
Introduction
Arsenic is a ubiquitous element in the crust of the earth. It is mainly transported in the environment by water. High arsenic level in groundwater has been observed in several countries in the world, and arseniasis is becoming an emerging epidemic in West Bengal of India and Bangladesh (Chen et al., 1999, Pontius et al., 1994). Arsenic has been used as a drug or poison for nearly 4000 years. The lethal effects of arsenic have long been documented. Many organs in gastrointestinal, dermal, nervous, renal, hepatic, hematopoietic, cardiovascular, respiratory, and ophthalmic systems are involved in acute and subacute toxicity of arsenic (Chen et al., 1997a). Long-term exposure to non-lethal dose of arsenic may induce chronic health hazards without a specific organotropism (Chen et al., 1997b). The systemic involvement of arsenic toxicity may result from the generalized distribution of ingested and inhaled arsenic in human body, and the direct toxic effect of inorganic arsenic and its methylated metabolites.
Despite the significant biological gradient of health hazards with arsenic exposure, only a small proportion of arsenic-exposed subjects are affected with arsenic-induced disorders. Furthermore, some were affected with arseniasis at low exposure level, some with high level. There seems to exist individual susceptibility to arseniasis. The specific aim of this report is to review a series of molecular epidemiological studies carried out to elucidate biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in Taiwan.
Section snippets
Arsenic-exposed areas and arsenic-induced health hazards in Taiwan
There are two endemic areas of long-term exposure to arsenic from drinking water as shown in Fig. 1. The southwestern endemic area includes townships of Putai, Ichu, Peimen, and Hsuehchia (Wu et al., 1989). Residents in this endemic area started using high-arsenic well water in the early 1910s. They shared few wells with their neighbors living in the same village. A public water supply system using surface water was implemented in this area since early 1960s, but its coverage remained low until
Biomarkers of arsenic-induced health hazards
The rapid progress of molecular biotechnology has accelerated the development of molecular epidemiology in recent two decades. Various biomarkers of exposure, effect, and susceptibility of human diseases have been identified and applied in epidemiological studies. These include the molecular dosimetry of internal dose and biologically effective dose of exposure to environmental risk factors; the characterization of early biological effects, altered structures and functions of target organs, and
Short-term (<1 year) internal dose: arsenic in urine, hair, and toenail
There are several biomarkers of short-term internal dose for ingested arsenic including levels of arsenic in blood, urine, hair, and finger or toe nails. In a study on 115 residents who were drinking arsenic-containing well water in northern Taiwan, biomarkers for internal dose of arsenic in urine, hair, and toenail were examined (Chiou et al., 1997a). The metabolites of inorganic arsenic including arsenite, arsenate, monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) in urine were
Reactive oxidants and antioxidant capability
In a study including 26 male and 38 female adult residents from the arsenic-exposed area in northeastern Taiwan (Wu et al., 2001), the blood level of arsenic was associated positively with plasma level of reactive oxidants determined by chemiluminescence method as well as negatively with antioxidant capability determined by azino-diethyl-benzthiozoline sulfate method. The findings suggest that arsenic may induce various health hazards through a mechanism of increasing oxidative stress.
Gene expression of inflammatory molecules
In a
Carotid atherosclerosis
Long-term exposure to ingested arsenic has been documented to induce atherosclerotic diseases including peripheral vascular disease, ischemic heart disease, and cerebral infarction in a dose-response relationship. A total of 199 male and 264 female adult residents from the southwestern arsenic-exposed in Taiwan were recruited to study the association between ingested arsenic and carotid atherosclerosis assessed by duplex ultrasonography (Wang et al., 2002). Three indices of long-term exposure
Serum carotene levels
In a nested case-control study on 16 skin cancer patients and 61 matched healthy resident in BFD-hyperendemic villages in southwestern Taiwan, an increased risk of arsenic-induced skin cancer was significantly associated with the decrease in serum β-carotene level (Hsueh et al., 1997). The relative risk of developing arsenic-induced skin cancer for those who had a serum β-carotene level ≤0.18 μg/mL was around 11-fold compared with those with a level >0.18 μg/mL. In a study on 29 BFD patients
Conclusion
Gene–gene and gene–environment interactions are involved in arsenic-induced cancers and cardiovascular diseases through toxicological mechanisms including genomic instability and oxidative stress. Further studies on associations among biomarkers including biologically effective dose, early biological effects, altered structures and functions of target organs, preclinical lesions, as well as acquired and genetic susceptibility will provide better understanding of pathogenesis of arsenic-induced
Acknowledgments
Supported by grants NSC 91-2320-B-002-075 and NSC 92-2320-B-002-135 from the National Science Council and DOH85-HR-503PL from the Department of Health, Executive Yuan, Taiwan.
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