Scientific Issues

At present, arsenic pollution is one of the key public health problems of China. The major scientific researches in recent years are introduced as follows.

Carcinogen Mechanism of Arsenic

Inorganic arsenic is an established human carcinogen and is associated with various tumors including lung, skin, and other internal cancers in exposed populations. However, generally accepted animal models for arsenic-induced cancers have not been demonstrated. Many studies have shown that arsenic can affect DNA repair and methylation, increase the generation of reactive oxygen species (ROS), activate the protooncogen such as c-myc, and so on, but none of these potential pathways have been convincingly accepted as the principal etiology (Abernathy et al., 1999). The carcinogenic mechanism of arsenic remains unclear.

Some recent evidences have suggested that certain genotoxic effects of arsenic may be mediated by ROS (Lee and Ho, 1995). In the endemic areas of Inner Mongolia, we have found that 8-hydroxy-2'-deoxyguanosine (8-OH-dG), one of the widely accepted sensitive markers of oxidative DNA damage, was excreted in the urine of arsenic exposed people. This is in accordance with the study by Matsui et al. (1999) which demonstrated that 8-OH-dG was significantly higher in people with arsenic-related skin neoplasms and arsenic keratosis. Our further analysis showed that of all the subjects examined, there were positive correlations of urine 8-OH-dG levels with total arsenic (tAs) and dimethylarsenic (DMeAs) levels in whole blood, respectively. What is more, increased urine 8-OH-dG levels correlated positively with the ratios of (MMeAs + DMeAs)/iAs in whole blood and negatively with the ratios of iAs/(MMeAs + DMeAs) in urine (MmeAs is monomethylarsenic and iAs is inorganic arsenic). 8-OH-dG is generally considered to be one of the main oxidative base damages to DNA, and may cause mutation (G: C to T:A) during DNA replication process. Therefore, we are now going deeply into the involvement of ROS and the role of 8-OH-dG in arsenic-related malignancies. Further studies will be carried out to clarify the dose-effect relationship between arsenic ingestion and 8-OH-dG in urine, blood and peripheral leukocyte of exposed population, and to determine whether 8-OH-dG can serve as a sensitive marker of arsenic exposure and arsenic-related malignancies.

Importance of Arsenic Ingestion in the Burning-Coal-Type Endemic Areas

It is generally reported that chronic endemic arsenism in China is caused either by drinking well water with high arsenic content or by breathing arsenic-containing burning coal. However, new information (Li et al., 1999) suggests that in addition to burning coal, nearly half of the total amount of arsenic is ingested from peppers. Peppers are one of the main foods of the residents in the endemic areas and are inclined to accumulate arsenic. So when residents dry peppers with coal rich in arsenic, peppers are contaminated with arsenic. The amount of pepper ingested there is about 10-30 g per person per day, hence about 0.5-1.5 mg arsenic per person per day is from pepper ingestion. It is an important source of arsenic exposure in Guizhou Province, China. For the prevention of arsenism, it is extremely necessary to change the residents' habit of drying peppers by burning coal rich in arsenic.

The Combined Toxicity of Fluoride and Arsenic

In some chronic endemic areas of arsenism, fluoride is also abundant in well water. The combined poisoning of fluoride and arsenic is of an exceptional type in China which has received interest all over the world. Some studies suggested that a synergistic interaction existed between the two elements. However, there is no consensus on the mechanism of the combined toxicity up to the present.

Children's Susceptibility

Children sometimes differ from adults in their susceptibility to hazardous chemicals. In studies of chronic arsenic exposure, children appeared to be more severely affected, probably due to a higher exposure per body weight. The characteristic skin lesions from arsenic have already shown in children of some regions in China. Moreover, the cases of hyperkeratosis in children are increasing remarkably in some regions we have investigated recently. Children's susceptibility to arsenic should be treated seriously.

Medical Usage ofArsenic

Whether arsenic is a trace element essential to human health remains a subject of debate. However, many studies have proved the potential beneficial effects of arsenic (ATSDR, 1998). In traditional Chinese medicine, the arsenic compound Xionghuang(AsS) was recorded as one of the superior materials in 'Bencaojing', a famous classic work of pharmacology written during the Ming dynasty. It is reported that arsenous acid or arsenic trioxide (As2O3) is effective in cosmetology, longevity and is often used against many diseases such as psoriasis, syphilis, rheumatosis, and trypanosomiasis (Chen et al., 1995). It was in the 1970s in China that As2O3 was introduced into the treatment of acute promyelicytic leukemia (APL) and it showed a striking effectiveness. A clinical complete remission rate was reported (Sun et al., 1992; Zhang et al., 1996) from 65.6% to 84% with treatment (10 mg/day, intravenous infusion for 29 to 60 days). In vitro studies suggested that As2O3 may induce the apoptosis of the NB4 cell by down-regulating the bcl-2 gene expression and altering the localization of PML-PARa/PML protein (Chen et al., 1996). In recent research in China it has also been observed that As2O3 can induce apoptosis in the cell lines of hepatocarcinoma. It is a medical breakthrough and may open a brand-new pathway in the treatment of malignancies.

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