Photomicronucleus assay of phototoxic and pseudophotoclastogenic chemicals in human keratinocyte NCTC2544 cells.

Abstract

Photochemical genotoxicity was evaluated in human keratinocyte NCTC2544 cells. The cells were pre-treated with photogenotoxic or pseudophotoclastogenic chemicals and irradiated with a solar-simulator for 50min at a total UV dose of 5J/cm(2) or placed in the dark for the same period. After washing, the cells were cultured for 1.5-2 cell cycles with fresh culture medium. At the end of culturing, slide specimens were prepared and examined for micronucleus formation. 8-Methoxypsoralen, a photogenotoxic chemical, strongly induced micronucleated cells with UV irradiation but not under non-irradiation conditions. Therefore, NCTC2544 cells were subjected to further investigation to evaluate the possible photogenotoxicity of other chemicals. 6-Methylcoumarin, 3,3',4',5-tetrachlorosalicylanilide and protoporphyrin IX disodium salt, which are all known phototoxic substances, induced micronucleated cells with irradiation but not in the non-irradiation state. These phototoxic substances were confirmed to be photogenotoxic. Tetrabenzoporphine and 5-aminolevulinic acid, which are used for photodynamic therapy, showed phototoxicity. However, these chemicals did not induce micronucleated cells in the irradiated or non-irradiated state, suggesting a lack of photogenotoxicity. Among 3 pseudophotoclastogenic chemicals having no light absorbance at 290-700nm, neither cycloheximide nor disulfoton induced micronucleated cells with or without irradiation; zinc oxide induced micronucleated cells with irradiation and, to a lesser extent, without irradiation. Based on the results of the photogenotoxicity assays of these 9 chemicals, NCTC2544 cells are considered to be a suitable test system to evaluate the photogenotoxic potential of chemicals.

• Authors: Mayumi Horinouchi, Sakae Arimoto-Kobayashi
• Journal: Mutation research (Mutat Res) Vol. 723 Issue 1 Pg. 43-50 (Jul 14 2011) ISSN: 0027-5107 [Print] Netherlands
• PMID: 21524715 (Publication Type: Evaluation Study, Journal Article)
• Copyright: Copyright © 2011 Elsevier B.V. All rights reserved.

Chemical References

• Protoporphyrins
• Salicylanilides
• protoporphyrin IX
• 3,3',4',5-tetrachlorosalicylanilide
• Methoxsalen

Topics

• Cell Line
• Dose-Response Relationship, Radiation
• Humans
• Keratinocytes (drug effects, radiation effects)
• Methoxsalen (toxicity)
• Micronucleus Tests (methods)
• Photochemotherapy (adverse effects)
• Protoporphyrins (toxicity)
• Salicylanilides (toxicity)
• Ultraviolet Rays (adverse effects)