title: Unventilated indoor coal-fired stoves in Guizhou province, China: cellular and genetic damage in villagers exposed to arsenic in food and air.
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.
  
  
  OBJECTIVE
  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 microg/L and 5.4-7.9 microg/g, respectively. These values were higher than those in the external control group, which had As concentrations of 46 microg/L for urine and 1.6 microg/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 mismatch 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.
authors: Department of Toxicology, School of Public Health, Guiyang Medical University, 9 Beijing Road, Guiyang City, 550004 Guizhou Province, People's Republic of China. aihuagy@yahoo.com.cn
authors: Aihua
authors: A
authors: Zhang
authors: Hong
authors: H
authors: Feng
authors: Guanghong
authors: G
authors: Yang
authors: Xueli
authors: X
authors: Pan
authors: Xianyao
authors: X
authors: Jiang
authors: Xiaoxin
authors: X
authors: Huang
authors: Xuexin
authors: X
authors: Dong
authors: Daping
authors: D
authors: Yang
authors: Yaxiong
authors: Y
authors: Xie
authors: Luo
authors: L
authors: Peng
authors: Li
authors: L
authors: Jun
authors: Changjun
authors: C
authors: Hu
authors: Li
authors: L
authors: Jian
authors: Xilan
authors: X
authors: Wang
mesh_terms: D016902:Air Pollution, Indoor / Q000009:adverse effects*; D001151:Arsenic / Q000032:analysis; D020261:Arsenic Poisoning / Q000235:genetics*; D001483:Base Sequence; D002280:Basal Cell Carcinoma / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D016022:Case-Control Studies; D019457:Chromosome Breakage; D003031:Coal; D003296:Cooking; D004249:DNA Damage; D004260:DNA Repair; D004781:Environmental Exposure; D005506:Food Contamination; D017353:Gene Deletion; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D012424:Rural Population; D012854:Sister Chromatid Exchange; D012878:Skin Neoplasms / Q000235:genetics; D014691:Ventilation
chemical_list: D003031:Coal; D001151:Arsenic