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Aihua Zhang,¹ Hong Feng,¹ Guanghong Yang,¹ Xueli Pan,¹ Xianyao Jiang,¹ Xiaoxin Huang,² Xuexin Dong,² Daping Yang,² Yaxiong Xie,¹ Luo Peng,¹ Li Jun,¹ Changjun Hu,¹ Li Jian,¹ and Xilan Wang¹

¹Department of Toxicology, School of Public Health, Guiyang Medical University, Guizhou, People's Republic of China; ²The 44^th Hospital of People's Liberation Army, Guizhou, People's Republic of China

Abstract
Background: Inorganic arsenic (iAs) is a well-known human carcinogen recognized by the World Health Organization and the International Agency for Research on Cancer. Currently, most iAs studies in populations are concerned with drinking water and occupational arsenicosis. In Guizhou province, arsenicosis caused by the burning of coal in unventilated indoor stoves is an unusual type of exposure. Because the poisoning mechanism involved in arsenicosis is as yet unknown and no effective therapy exists, progress has been slow on the prevention and therapy of arsenicosis.

Objectives: We examined the relationship between arsenic (As) exposure from the burning of coal in unventilated indoor stoves and genetic damage in humans, using cellular and molecular indices. We selected villagers from Jiaole township, Guizhou province, China, who had been exposed to milligram levels of As daily via food and air contaminated by the burning of As-containing coal in unventilated indoor stoves.

Results: The As-exposed subjects from Jiaole were divided into four groups according to skin lesion symptoms: nonpatients, mild, intermediate, and severe arsenicosis. Another 53 villagers from a town 12 km from Jiaole were recruited as the external control group. In the four groups of exposed subjects, As concentrations in urine and hair were 76–145 µg/L and 5.4–7.9 µg/g, respectively. These values were higher than those in the external control group, which had As concentrations of 46 µg/L for urine and 1.6 µg/g for hair. We measured sister chromatid exchange and chromosomal aberrations to determine human chromosome damage, and for DNA damage, we measured DNA single-strand breaks and DNA–protein cross-links. All measurements were higher in the four exposed groups compared with the external control group. DNA repair was impaired by As exposure, as indicated by the mRNA of O-6-methylguanine-DNA methyltransferase (MGMT) , X-ray repair complementing defective repair in Chinese hamster cells 1 (XRCC1) , and, to a lesser extent, by the mis-match repair gene hMSH2 mRNA. The expression of mutant-type p53 increased with aggravation of arsenicosis symptoms, whereas the expression of p16-INK4(p16) decreased. p53 mutated at a frequency of 30–17% in the carcinoma (n = 10) and precarcinoma (n = 12) groups. No mutation was found in p16, although deletion was evident. Deletion rates were 8.7% (n = 23) and 38.9% (n = 18) in noncarcinoma and carcinoma groups, respectively.

Conclusions: The results showed that long-term As exposure may be associated with damage of chromosomes and DNA, gene mutations, gene deletions, and alterations of DNA synthesis and repair ability.

Key words: arsenic, coal, genetic damage, toxicity. Environ Health Perspect 115:653–658 (2007) . doi:10.1289/ehp.9272 available via http://dx.doi.org/ [Online 9 January 2007]

This article is part of the mini-monograph "Arsenic Occurrence and Health Effects in China."

Address correspondence to A. Zhang, Department of Toxicology, School of Public Health, Guiyang Medical University, 9 Beijing Rd., Guiyang City, 550004, Guizhou Province, People's Republic of China. Telephone: 86 8517899882. Fax: 86 851 6908908. E-mail: aihuagy@yahoo.com.cn

We acknowledge Xinren Hygienic and Anti-Epidemic Station for assistance in the investigation. In particular, we thank S. Qin, F. Xue, D. Zhou, J. Qiu, Z. Zheng, A. Zhu, and Y. Zhou. Y. Zheng provided comments during manuscript preparation. We also thank the villagers from Xinren county for their participation and cooperation in this investigation.

This work was supported by Chinese National Natural Science Foundation grants 39660070, 30060077, and 30460123, and by the Guizhou Natural Science Foundation.

The authors declare they have no competing financial interests.

Received 17 April 2006 ; accepted 3 January 2007.