Arsenic-induced genotoxic and cytotoxic effects in human keratinocytes, melanocytes and dendritic cells.
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.
Graham-Evans
Barbara
B
Molecular Toxicology Research Laboratory, NIH-Center for Environmental Health, Jackson State University, Jackson, MS 39217, USA.
Cohly
Hari H P
HH
Yu
Hongtao
H
Tchounwou
Paul B
PB
D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D020552:Comet Assay; D003713:Dendritic Cells / Q000187:drug effects* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004785:Environmental Pollutants / Q000633:toxicity; D015603:Keratinocytes / Q000187:drug effects* / Q000473:pathology; D008544:Melanocytes / Q000187:drug effects* / Q000473:pathology; D010087:Oxides / Q000633:toxicity*
D001152:Arsenicals; D004785:Environmental Pollutants; D010087:Oxides; D000077237:Arsenic Trioxide