Establishment Op a Steain of Human Skin Cells on Chemically Defined Medium NCTC 109

Bakken, Paul C.; Evans, Virginia J.; Earle, Wilton R.; Stevenson, Robert E.

doi:10.1093/oxfordjournals.aje.a120170

Cited by 10 publications

(7 citation statements)

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“…Gelardi et al ( 2001 ) reported that in the human breast skin keratinocyte-derived cell line NCTC 2544 (Bakken et al 1961 ) the prototypic CYP activities ECOD, EROD, and PROD were easily detectable in basal conditions and were susceptible to the classical CYP inducers β-naphthoflavone, 3-MC and phenobarbital, and to the classical CYP inhibitors α-naphthoflavone and metyrapone.…”

Section: Xenobiotic-metabolizing Enzymes In the Human Skin Including mentioning

confidence: 99%

Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models

Oesch¹,

Fabian

Guth

et al. 2014

Arch Toxicol

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The exposure of the skin to medical drugs, skin care products, cosmetics, and other chemicals renders information on xenobiotic-metabolizing enzymes (XME) in the skin highly interesting. Since the use of freshly excised human skin for experimental investigations meets with ethical and practical limitations, information on XME in models comes in the focus including non-human mammalian species and in vitro skin models. This review attempts to summarize the information available in the open scientific literature on XME in the skin of human, rat, mouse, guinea pig, and pig as well as human primary skin cells, human cell lines, and reconstructed human skin models. The most salient outcome is that much more research on cutaneous XME is needed for solid metabolism-dependent efficacy and safety predictions, and the cutaneous metabolism comparisons have to be viewed with caution. Keeping this fully in mind at least with respect to some cutaneous XME, some models may tentatively be considered to approximate reasonable closeness to human skin. For dermal absorption and for skin irritation among many contributing XME, esterase activity is of special importance, which in pig skin, some human cell lines, and reconstructed skin models appears reasonably close to human skin. With respect to genotoxicity and sensitization, activating XME are not yet judgeable, but reactive metabolite-reducing XME in primary human keratinocytes and several reconstructed human skin models appear reasonably close to human skin. For a more detailed delineation and discussion of the severe limitations see the “Overview and Conclusions” section in the end of this review.

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Section: Xenobiotic-metabolizing Enzymes In the Human Skin Including mentioning

confidence: 99%

Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models

Oesch¹,

Fabian

Guth

et al. 2014

Arch Toxicol

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“…Therefore, the aim of this study was the characterization of the xenobiotic metabolizing activities of native human skin compared with in vitro models such as (i) the commercially available 3D epidermal model EpiDerm™ (EPI‐200; MatTek MatTek Corporation) based on human primary keratinocytes and (ii) several human skin‐derived cell monolayers. The latter one including the well‐known keratinocyte‐based cell lines, HaCaT (19) and NCTC 2544 (20) as well as primary human epidermal keratinocytes (NHEK). For use in dermatotoxicology, it is necessary that alternative testing methods reproduce xenometabolic pathways of human skin so that the results of in vitro testing are meaningful.…”

Section: Introductionmentioning

confidence: 99%

Xenobiotic metabolism capacities of human skin in comparison with a 3D epidermis model and keratinocyte‐based cell culture as in vitro alternatives for chemical testing: activating enzymes (Phase I)

Götz

Pfeiffer

Tigges

et al. 2012

Experimental Dermatology

103

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Skin is important for the absorption and metabolism of exposed chemicals such as cosmetics or pharmaceuticals. The Seventh Amendment to the EU Cosmetics Directive prohibits the use of animals for cosmetic testing for certain endpoints, such as genotoxicity; therefore, there is an urgent need to understand the xenobiotic metabolizing capacities of human skin and to compare these activities with reconstructed 3D skin models developed to replace animal testing. We have measured Phase I enzyme activities of cytochrome P450 (CYP) and cyclooxygenase (COX) in ex vivo human skin, the 3D skin model EpiDermÔ (EPI-200), immortalized keratinocyte-based cell lines and primary normal human epidermal keratinocytes. Our data demonstrate that basal CYP enzyme activities are very low in whole human skin and EPI-200 as well as keratinocytes. In addition, activities in monolayer cells differed from organotypic tissues after induction. COX activity was similar in skin, EPI-200 and NHEK cells, but was significantly lower in immortalized keratinocytes. Hence, the 3D model EPI-200 might represent a more suitable model for dermatotoxicological studies. Altogether, these data help to better understand skin metabolism and expand the knowledge of in vitro alternatives used for dermatotoxicity testing.Abbreviations: CYP, cytochrome P450-monooxygenase; COX, cyclooxygenase; PGE 2, prostaglandin E2; 3-MC, 3-methylcholanthrene; EPI-200, reconstituted epidermis model EpiDermÔ (MatTek); NHEK, normal human keratinocytes; HLM, human liver microsomes.

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“…To better understand the resemblance of in vitro models, as used, for example, in sunscreen testing (6), for metabolic potential of human skin, we here assessed phase II enzyme activities in human ex vivo skin and keratinocyte‐derived skin models: a commercially available 3D epidermal model (EPI‐200, MatTek Corp., Ashland, MA, USA) that is based on primary keratinocytes, HaCaT keratinocytes (7), NCTC 2544 cells (8) as well as primary normal human epidermal keratinocytes (NHEK). While phase I enzyme activities may determine activation and toxification of compounds as is discussed in our corresponding publication, this phase II paper (part two) assesses mainly, though not solely, detoxification capacities of human skin and epidermal in vitro models.…”

Section: Introductionmentioning

confidence: 99%

Xenobiotic metabolism capacities of human skin in comparison with a 3D‐epidermis model and keratinocyte‐based cell culture as in vitro alternatives for chemical testing: phase II enzymes

Götz

Pfeiffer

Tigges

et al. 2012

Experimental Dermatology

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The 7th Amendment to the EU Cosmetics Directive prohibits the use of animals in cosmetic testing for certain endpoints, such as genotoxicity. Therefore, skin in vitro models have to replace chemical testing in vivo. However, the metabolic competence neither of human skin nor of alternative in vitro models has so far been fully characterized, although skin is the first‐pass organ for accidentally or purposely (cosmetics and pharmaceuticals) applied chemicals. Thus, there is an urgent need to understand the xenobiotic‐metabolizing capacities of human skin and to compare these activities to models developed to replace animal testing. We have measured the activity of the phase II enzymes glutathione S‐transferase, UDP‐glucuronosyltransferase and N‐acetyltransferase in ex vivo human skin, the 3D epidermal model EpiDerm 200 (EPI‐200), immortalized keratinocyte‐based cell lines (HaCaT and NCTC 2544) and primary normal human epidermal keratinocytes. We show that all three phase II enzymes are present and highly active in skin as compared to phase I. Human skin, therefore, represents a more detoxifying than activating organ. This work systematically compares the activities of three important phase II enzymes in four different in vitro models directly to human skin. We conclude from our studies that 3D epidermal models, like the EPI‐200 employed here, are superior over monolayer cultures in mimicking human skin xenobiotic metabolism and thus better suited for dermatotoxicity testing.

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Establishment Op a Steain of Human Skin Cells on Chemically Defined Medium NCTC 109

Cited by 10 publications

References 0 publications

Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models

Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models

Xenobiotic metabolism capacities of human skin in comparison with a 3D epidermis model and keratinocyte‐based cell culture as in vitro alternatives for chemical testing: activating enzymes (Phase I)

Xenobiotic metabolism capacities of human skin in comparison with a 3D‐epidermis model and keratinocyte‐based cell culture as in vitro alternatives for chemical testing: phase II enzymes

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