Wu Huijie, Manonmanii K, Lam Paul K S, Huang Shu-Huei, Wang Jian Ping, Ng Jack C
National Research Centre for Environmental Toxicology (EnTox), The University of Queensland, 39 Kessels Road, Coopers Plains, Brisbane, Queensland 4108, Australia.
Toxicol Lett. 2004 Dec 1;154(1-2):149-57. doi: 10.1016/j.toxlet.2004.08.005.
Arsenic has been classified as a human carcinogen based on epidemiological data however the mechanism of its carcinogenicity is still unclear. Urinary biomarkers for chronic arsenic exposure would be valuable as an early warning indicator for timely interventions. In this study, young female C57Bl/6J mice were given drinking water containing 0, 100, 250 and 500 microg Asv/L as sodium arsenate ad libitum for 12 months. Urine was collected bimonthly for urinary arsenic methylation assay and porphyrin analysis. All detectable arsenic species showed strong linear correlation with administered dosage and the arsenic methylation patterns were similar in all three treatment groups. No significant changes of methylation patterns were observed over time for either the control or test groups. Urinary coproporphyrin III was significantly increased in the 8th month in 250 and 500 microg/L groups and remained significantly dose-related after 10 and 12 months. Coproporphyrin I also showed a significant dose-response relationship after 12 months. Our results confirm that urinary arsenic is a useful biomarker for internal dose. The alteration of porphyrin profile suggests that arsenic can affect the heme metabolism and this may occur prior to the onset of arsenic induced carcinogenesis.
基于流行病学数据，砷已被归类为人类致癌物，但其致癌机制仍不清楚。慢性砷暴露的尿液生物标志物作为早期预警指标，对于及时干预具有重要价值。在本研究中，给年轻雌性C57Bl/6J小鼠随意饮用含0、100、250和500微克五价砷/升的砷酸钠水溶液，持续12个月。每两个月收集尿液进行尿砷甲基化测定和卟啉分析。所有可检测到的砷物种与给药剂量呈强线性相关，且三个治疗组的砷甲基化模式相似。对照组和试验组的甲基化模式随时间均未观察到显著变化。在第8个月时，250和500微克/升组的尿粪卟啉原III显著增加，在10个月和12个月后仍与剂量显著相关。12个月后，粪卟啉I也显示出显著的剂量反应关系。我们的结果证实，尿砷是体内剂量的有用生物标志物。卟啉谱的改变表明砷可影响血红素代谢，这可能在砷诱导的致癌作用开始之前就已发生。
