ABSTRACT
There is an urgent need to validate in vitro human skin models for use in safety testing. An important component of validation is characterizing the metabolizing capacity of these models. We report comparison of the expression of 139 genes encoding xenobiotic metabolizing enzymes in the EpiDerm model and human skin. In microarray analysis, the expression of 87% of the genes was consistent between the EpiDerm model and human skin indicating the presence of similar metabolic pathways suggesting commonality in function. Analysis of EpiDerm models constructed from four donors showed highly comparable expression of xenobiotic metabolizing genes demonstrating reproducibility of the model. Overall, the expression of Phase II enzymes appeared to be more pronounced in human skin and the EpiDerm model than that of Phase I enzymes, consistent with the role of skin in detoxification of xenobiotics. Though the basal expression of CYPs in particular was low in EpiDerm, significant induction of CYP1A1/1B1 activity was observed following treatment with 3-methylcholanthrene. These results indicate that the xenobiotic metabolizing capacity of the EpiDerm model appears to be representative of human skin. Models such as EpiDerm provide a valuable in vitro approach for evaluation of metabolism and toxicity of cutaneous exposures to xenobiotics.
Subject(s)
Epidermis/metabolism , Gene Expression/drug effects , Models, Biological , Skin/metabolism , Xenobiotics/metabolism , Adolescent , Biotransformation , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 Enzyme System/metabolism , Enzyme Induction/drug effects , Epidermis/drug effects , Epidermis/enzymology , Female , Glucuronosyltransferase/metabolism , Glutathione Transferase/metabolism , Humans , In Vitro Techniques , Inactivation, Metabolic , Oligonucleotide Array Sequence Analysis , Skin/drug effects , Skin/enzymology , Xenobiotics/toxicity , Young AdultABSTRACT
A total of twenty-six allozyme loci were assayed in six crayfish species. Estimated mean heterozygosity was low (5.5 percent) for all species in comparison with the invertebrate average. The specific values, however, ranged from 2.9 percent to 8.3 percent. These crayfish estimates are consistent with estimates for other decapods where low heterozygosity is the rule. The consistency of low heterozygosity estimates in the order Decapoda suggests that its explanation may include both order specific differences such as low mutation or intracistronic recombination rates and species specific differences. A dendrogram, constructed using Nei's D, is in agreement with the morphological clustering.
