Assessment of toxic potential of industrial chemicals using a cultured human bioartificial skin model: production of interleukin 1alpha and hydroxyeicosatetraenoic acids.
Cytotoxicity assays using artificial skin are proposed as alternative methods for in vitro tests to minimize animals used in ocular and dermal irritation testing. The responses of the artificial skins were studied to a well-characterized chemical irritant, such as toluene, glutaraldehyde and sodium lauryl sulfate (SLS), and a nonirritant, such as polyethylene glycol. The evaluation of irritating and nonirritating test chemicals was also compared with responses seen in human dermal fibroblasts and human epidermal keratinocytes grown in monolayer culture. The responses monitored included the MTT mitochondrial functionality assay. In order to better understand the local mechanisms involved in skin damage and repair, the productions of several mitogenic proinflammatory mediators such as interleukin-1alpha (IL-1alpha), 12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE were investigated. Dose-dependent increases in the levels of IL-1alpha and HETEs were observed in the underlying medium of the skin systems exposed to two skin irritants, glutaraldehyde and SLS. The results of the present study show that both human artificial skins can be used as efficient testing models for the evaluation of skin toxicity in vitro and for screening the contact skin irritancy in vitro.
Laboratory of Tissue Engineering, Department of Chemical Engineering, Dongguk University, Seoul, Korea.
E K
EK
Yang
H H
HH
Yoon
D H
DH
Lee
J K
JK
Park
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000096:biosynthesis*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005976:Glutaral / Q000633:toxicity; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000096:biosynthesis*; D011092:Polyethylene Glycols / Q000633:toxicity; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D017768:Skin, Artificial; D012967:Sodium Dodecyl Sulfate / Q000633:toxicity; D014050:Toluene / Q000633:toxicity
D006893:Hydroxyeicosatetraenoic Acids; D007375:Interleukin-1; D012967:Sodium Dodecyl Sulfate; D014050:Toluene; D011092:Polyethylene Glycols; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D005976:Glutaral