Induction of Neonatal Rat Skin and Liver Aryl Hydrocarbon Hydroxylase by Coal Tar and Its Constituents

Bickers, David R.; Wróblewski, David; Tapu-Dutta-Choudhury,; Mukhtar, Hasan

doi:10.1111/1523-1747.ep12506525

Cited by 26 publications

(9 citation statements)

References 16 publications

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“…The epidermis could then be easily peeled off in a single strip with fine forceps. Alternatively, the skin sections were placed in phosphatebuffered saline containing 10 mM dithiothreitol for 2 h, after which the epidermis was removed and rinsed free of dithiothreitol (20).…”

Section: Methodsmentioning

confidence: 99%

Functional Expression and Cellular Localization of a Mouse Epidermal Lipoxygenase

Funk

Keeney

Oliw

et al. 1996

Journal of Biological Chemistry

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Three distinct murine lipoxygenase genes have been functionally characterized: 5-lipoxygenase (Chen, X.-S., Naumann, T. A., Kurre, U. , Jenkins, N. A., Copeland, N. G., and Funk, C. D. (1995) J. Biol. Chem. 270, 17993-17999), platelet-type 12-lipoxygenase and leukocyte-type 12-lipoxygenase (Chen, X.-S., Kurre, U., Jenkins, N. A., Copeland, N. G., and Funk, C. D. (1994) J. Biol. Chem. 269, 13979-13987). Here, we describe the cloning and functional characterization of a fourth lipoxygenase gene in mice. Using a polymerase chain reaction-based approach together with partial sequence information from a genomic clone, we isolated a novel lipoxygenase cDNA from the RNA of 3-6-day-old mouse epidermis. The open reading frame predicts a 662-amino acid lipoxygenase that displays 60% identity with both murine 12-lipoxygenase isozymes and 40% identity to 5-lipoxygenase; the sequence is identical to a genomic sequence reported recently (van Dijk, K. W., Steketee, K., Havekes, L., Frants, R., and Hofker, M. (1995) Biochim. Biophys. Acta 1259, 4-8). A full-length clone was expressed in human embryonic kidney 293 cells and homogenates from disrupted cells produced 12-hydroxyeicosatetraenoic acid (12-HETE) and minor amounts of 15-HETE from arachidonic acid. Chiral phase analysis indicated that the 12-HETE is exclusively the 12S enantiomer. In situ hybridization revealed highly specific expression of epidermal lipoxygenase in differentiated keratinocytes of the epidermis and in restricted regions of the root sheath and bulb of hair follicles. High expression was also detected in conjunctiva of the eyelid and in cells of Meibomian and preputial (sebaceous) glands. A 2. 4-kilobase mRNA was detected in mouse epidermis by Northern blot analysis and its abundance was not affected by phorbol ester treatment. The epidermal lipoxygenase gene (Aloxe) resides on mouse chromosome 11 closely linked with the two 12-lipoxygenase genes (Alox12p and Alox12l).

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Section: Methodsmentioning

confidence: 99%

Functional Expression and Cellular Localization of a Mouse Epidermal Lipoxygenase

Funk

Keeney

Oliw

et al. 1996

Journal of Biological Chemistry

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“…The rate of increase in the enzyme activity, however, was much greater in skin as compared to the other tissues [35], These studies established that even though the specific enzyme activities occur at much lower levels in the skin as compared to that in the liver, they may make a major contribution in the overall metabolism of xenobiotics in the body. Several other reports from our labo ratory further demonstrated the induction of cutaneous AHH, ECOD and EROD activities in animal models, by a number of agents gen erally used in the therapy of skin-related dis orders [36][37][38][39],…”

Section: Ah H Activity In Skinmentioning

confidence: 99%

Cytochrome P-450 and Drug Development for Skin Diseases

Ahmad

Agarwal²,

Mukhtar³

1996

Skin Pharmacol Physiol

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Cytochromes P-450 (CYPs) are the most versatile and important class of drug-metabolizing enzymes which are induced in mammalian skin in response to xenobiotic exposure. CYPs are the target of special interest in the development of pharmaceuticals for skin diseases because most, if not all, drugs available in the armamentarium of the dermatologist are substrates, inducers or inhibitors of this enzyme family. The functional significance of drug metabolism in the skin and the implication of CYP in skin pathology and therapy is an area for future investigation. A detailed insight into the mechanism of action of various cutaneous CYPs, being capable of modulating the drug bioavailability, will be helpful in the development of better strategies for novel therapy against constantly increasing skin disorders. This brief review puts some of these perspectives together and suggests additional research in the area of CYPs with regard to their expression and modulation in mammalian skin as well as their implication in dermatological disorders and the therapy of skin diseases.

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“…Effect of cutaneously applied Coal Tar on AHH in neonatal rats (Bickers et al 1982). excreted by all groups of animals maintained on a Coal Tar diet.…”

Section: Tablementioning

confidence: 99%

Final Safety Assessment of Coal Tar as Used in Cosmetics

2008

Int J Toxicol

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Coal Tar is a semisolid by-product obtained in the destructive distillation of bituminous coal, which functions in cosmetic products as a cosmetic biocide and denaturant--antidandruff agent is also listed as a function, but this is considered an over-the-counter (OTC) drug use. Coal Tar is a nearly black, viscous liquid, heavier than water, with a naphthalene-like odor and a sharp burning taste, produced in cooking ovens as a by-product in the manufacture of coke. Crude Coal Tar is composed of 48% hydrocarbons, 42% carbon, and 10% water. In 2002, Coal Tar was reported to the Food and Drug Administration (FDA) to be used in four formulations, all of which appear to be OTC drug products. Coal Tar is monographed by the FDA as Category I (safe and effective) OTC drug ingredient for use in the treatment of dandruff, seborrhoea, and psoriasis. Coal Tar is absorbed through the skin of animals and humans and is systemically distributed. In short-term studies, mice fed a diet containing Coal Tar found it unpalatable, but no adverse effects were reported other than weight loss; rats injected with Coal Tar experienced malaise in one study and decreased water intake and increased liver weights in another; rabbits injected with Coal Tar residue experienced eating avoidance, respiratory difficulty, sneezing, and weight loss. In a subchronic neurotoxicity study using mice, a mixture of phenols, cresols, and xylenols at concentrations approximately equal to those expected in Coal Tar extracts produced regionally selective effects, with a rank order of corpus striatum > cerebellum > cerebral cortex. Coal Tar applied to the backs of guinea pigs increases epidermal thickness. Painting female rabbits with tar decreases the absolute and relative weights of the ovaries and decreased the number of interstitial cells in the ovary. Four therapeutic Coal Tar preparations used in the treatment of psoriasis were mutagenic in the Ames assay. Urine and blood from patients treated with Coal Tar were genotoxic in bacterial assays. Coal Tar was genotoxic in a mammalian genotoxicity assay and induced DNA adducts in various tissue types. Chronic exposure of mice to Coal Tar significantly decreased survival and liver neoplasms were seen in a significant dose-related trend; in other studies using mice lung tumors and perianal skin cancers were found. Coal Tar was comedogenic in three small clinical studies. Folliculitis is associated with the prolonged use of some tars. Several published reports describe cases of contact sensitivity to Coal Tar. Polycyclic aromatic hydrocarbons, which make up Coal Tar, are photosensitizers and cause phototoxicity by an oxygen-dependent mechanism. A retrospective study of the reproductive toxicity of Coal Tar in humans compared exposed women to controls and found little difference in spontaneous abortion and congenital disorders. Cancer epidemiology studies of patients who have received Coal Tar therapy of one form or other have failed to link treatment with an increase in the risk of cancer. Although the Cosmetic In...

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Induction of Neonatal Rat Skin and Liver Aryl Hydrocarbon Hydroxylase by Coal Tar and Its Constituents

Cited by 26 publications

References 16 publications

Functional Expression and Cellular Localization of a Mouse Epidermal Lipoxygenase

Functional Expression and Cellular Localization of a Mouse Epidermal Lipoxygenase

Cytochrome P-450 and Drug Development for Skin Diseases

Final Safety Assessment of Coal Tar as Used in Cosmetics

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