Increased damage of exon 5 of p53 gene in workers from an arsenic plant.
Mutagenesis is a multistage process. Substitution mutations can be induced by base modified through alteration of pairing property. Mutations of exon 5 and 8 of p53 gene have been found in most arsenicosis patients with precarcinomas and carcinomas, but never in arsenicosis individuals without precarcinomas and carcinomas. This study investigates whether base modification exists in exon 5 and 8 of p53 gene, and explores the dose-effect relationship between damage of exon 5 of p53 gene and urinary arsenic. Concentrations of urinary 8-hydroxydeoxyguanine (8-OHdG) are analyzed to identify the occurrence of DNA damage. The real-time PCR developed by Sikorsky et al. is applied to detect base modification in exon 5 and 8 of p53 gene for apparently healthy participants. Our results show that the mean total arsenic concentrations of two exposed groups from an arsenic plant are significantly elevated compared with the control group, and the damage level of exon 5 of the high-exposed group is significantly higher than that of the control group, but which does not happen in exon 8. The closely correlation between the damage index of exon 5 and urinary organic arsenic concentration are found. Concentration of 8-OHdG of the high-exposed group is significantly higher than that of the control group. These results imply that base modification in exon 5 of p53 gene can be induced by arsenic. In addition, our study suggests that the damage level of exon 5 is a useful biomarker to assess adverse health effect levels caused by chronic exposure to arsenic.
Wen
Weihua
W
Department of Occupational Health, Yunnan Provincial Center for Disease Control and Prevention, No. 158, Dongsi Street, Xishan District, Kunming, Yunnan 650022, People's Republic of China. huawen123@163.com
Che
Wangjun
W
Lu
Lin
L
Yang
Jun
J
Gao
Xufang
X
Wen
Jinghua
J
Heng
Zhengchang
Z
Cao
Shuqiao
S
Cheng
Huirong
H
D000080242:8-Hydroxy-2'-Deoxyguanosine / Q000031:analogs & derivatives; D020261:Arsenic Poisoning / Q000235:genetics* / Q000652:urine; D001152:Arsenicals / Q000009:adverse effects*; D016022:Case-Control Studies; D004249:DNA Damage / Q000187:drug effects*; D005091:Exons / Q000235:genetics*; D006147:Guanine / Q000031:analogs & derivatives / Q000652:urine; D006801:Humans; D016273:Occupational Exposure; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D001152:Arsenicals; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D006147:Guanine; C078307:8-oxo-7,8-dihydrodeoxyguanine; D000080242:8-Hydroxy-2'-Deoxyguanosine