Graham-Evans Barbara, Cohly Hari H P, Yu Hongtao, Tchounwou Paul B
Molecular Toxicology Research Laboratory, NIH-Center for Environmental Health, Jackson State University, Jackson, MS 39217, USA.
Int J Environ Res Public Health. 2004 Sep;1(2):83-9. doi: 10.3390/ijerph2004020083.
Arsenical keratosis and skin cancer are among the most common health effects associated with acute and chronic exposures to arsenic. This study examines the acute and chronic dose-responses of arsenic in established human cell lines using keratinocytes (HaCaT), melanocytes (CRL1675) and dendritic cells (THP-1 + A23187). Chronic conditions were established by treating the three cell lines with at least 8 passages in 0.2 microg/mL arsenic trioxide. Cytotoxicity was assessed using the fluorescein diacetate assay after 72 hrs of exposure. Single cell gel electrophoresis (Comet assay) was used to measure DNA damage. Acute exposure to arsenic had LD10 and LD25 values of 0.38 microg/mL and 3.0 microg/mL for keratinocytes; 0.19 microg/mL and 0.38 microg/mL for melanocytes; and 0.38 microg/mL and 0.75 microg/mL for dendritic cells. Cytotoxicity assays for chronically exposed cells resulted in LD10, and LD25 values of 0.4 microg/mL and 0.8 microg/mL for keratinocytes; 0.10 microg/mL and 0.20 microg/mL for melanocytes; and 0.10 microg/mL and 1.0 microg/mL for dendritic cells. The Comet assay showed that arsenic was highly genotoxic to the three cell lines. No significant differences (p > 0.05) in DNA cleavage were observed between acute and chronic exposures. In acute exposure arsenic genotoxicity was more severe with dendritic cells while melanocytes were more sensitive to arsenic cytotoxicity. Similarly, chronically exposed dendritic cells showed the maximum genotoxic damage while melanocytes were more sensitive to arsenic cytotoxicity. In conclusion, this research shows that arsenic is dermatotoxic, showing a high degree of genotoxicity and cytotoxicity to skin cells.
砷角化病和皮肤癌是与急性和慢性砷暴露相关的最常见健康影响。本研究使用角质形成细胞（HaCaT）、黑素细胞（CRL1675）和树突状细胞（THP - 1 + A23187），研究已建立的人类细胞系中砷的急性和慢性剂量反应。通过在0.2微克/毫升三氧化二砷中对三种细胞系进行至少8次传代来建立慢性条件。暴露72小时后，使用荧光素二乙酸酯测定法评估细胞毒性。单细胞凝胶电泳（彗星试验）用于测量DNA损伤。角质形成细胞急性暴露于砷时，LD10和LD25值分别为0.38微克/毫升和3.0微克/毫升；黑素细胞为0.19微克/毫升和0.38微克/毫升；树突状细胞为0.38微克/毫升和0.75微克/毫升。对长期暴露细胞的细胞毒性测定结果显示，角质形成细胞的LD10和LD25值分别为0.4微克/毫升和0.8微克/毫升；黑素细胞为0.10微克/毫升和0.20微克/毫升；树突状细胞为0.10微克/毫升和1.0微克/毫升。彗星试验表明，砷对这三种细胞系具有高度遗传毒性。急性和慢性暴露之间在DNA切割方面未观察到显著差异（p>0.05）。在急性暴露中，砷对树突状细胞的遗传毒性更严重，而黑素细胞对砷的细胞毒性更敏感。同样，长期暴露的树突状细胞显示出最大的遗传毒性损伤，而黑素细胞对砷的细胞毒性更敏感。总之，本研究表明砷具有皮肤毒性，对皮肤细胞表现出高度的遗传毒性和细胞毒性。
