National Research Centre for Environmental Toxicology, The University of Queensland, Brisbane, Queensland, Australia.
Kaohsiung J Med Sci. 2011 Sep;27(9):417-23. doi: 10.1016/j.kjms.2011.05.010. Epub 2011 Aug 23.
Arsenic is a proven human carcinogen. Although the mechanism of its carcinogenicity is still largely unknown, methylation is thought to have an important role to play in arsenic toxicity. In this study, urinary methylation profiles were investigated in female C57BL/6J black mice given drinking water containing 500 μg arsenate (As(V))/L, 250 μg As(V)/L, or 100 μg As(V)/L as sodium arsenate for 2 months. The concentrations of arsenic chosen reflected those in the drinking water often encountered in arsenic-endemic areas. Urine samples were collected from the mice at the end of the exposure period, and the arsenic species were analyzed by high performance liquid chromatography-inductively coupled plasma-mass spectrometry. All detectable arsenic species showed strong linear correlation with the administered dosage. The methylation patterns were similar in all three groups with a slight decrease of dimethylarsinic acid/As(V) ratio in the 500-μg/L group, which corresponded to the significantly higher arsenic retention in the tissue. The results indicate that urinary arsenic could be used as a good biomarker for internal dose and potential biological effects. Different doses of arsenic exposure could result in different degrees of methylation, excretion, and tissue retention, and this may contribute to the understanding of arsenic carcinogenicity.
砷是一种已被证实的人类致癌物。虽然其致癌机制在很大程度上仍不清楚,但甲基化被认为在砷毒性中起着重要作用。在这项研究中,给予饮用水中含有 500μg/L 砷酸盐(As(V))、250μg/L As(V)或 100μg/L As(V)作为砷酸钠的雌性 C57BL/6J 黑鼠,研究了其 2 个月的尿液甲基化谱。所选砷浓度反映了砷污染地区饮用水中常见的浓度。在暴露期结束时从小鼠中收集尿液样本,并通过高效液相色谱-电感耦合等离子体质谱法分析砷形态。所有可检测到的砷形态与所给予的剂量均呈强线性相关。所有三组的甲基化模式相似,500μg/L 组二甲基砷酸/As(V)比值略有下降,这与组织中砷的保留量明显更高相对应。结果表明,尿砷可作为内剂量和潜在生物学效应的良好生物标志物。不同剂量的砷暴露可能导致不同程度的甲基化、排泄和组织保留,这可能有助于理解砷的致癌性。