Assessment of the acute toxicity and potential irritancy of hair dye constituents.
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Administration, Oral↗
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Toxicity of HC Orange No. 1 to Daphnia magna, zebrafish (Brachydanio rerio) embryos, and goldfish (Carassius auratus).
HC Orange No. 1 (HCO1; 2-nitro-4'-hydroxydiphenylamine) (CAS No. 54381-08-7) is used as a color additive in hair dyes and can be released into aquatic environments in wastewater. In this paper, the effects of HCO1 on aquatic organisms were studied using a battery of toxicological tests. These included measuring immobilization of Daphnia magna, inhibition of zebrafish embryo development, and acute lethality in zebrafish and goldfish, which are different species belonging to different trophic levels. HCO1 was toxic to all of the organisms studied. In our experiments, HCO1 remarkably restrained the mobility of D. magna, which may cause subsequent death. The EC50 value for restrained the mobility of D. magna at 48 h was 1.54 mg HCO1 l(-1). In addition, HCO1 showed toxicity in zebrafish and goldfish, where LC50 values at 96 h were 4.04 and 5.37 mg l(-1), respectively. The results also indicated that HCO1 remarkably retarded the development of zebrafish embryos, which may cause embryo abnormality and even lethality. The most sensitive toxicological endpoint in the development of the embryos was failure to hatch, which had an EC50 of 0.19 mg HCO1 l(-1). These results indicated that HCO1 is a potential teratogen to zebrafish embryos. In addition, as HCO1 concentrations increased, the outcomes of each of these toxicity tests changed in a concentration-dependent manner. Together, the results revealed that HCO1 appears to be toxic to multiple different species of aquatic organisms. The EC50 (LC50) values contain sufficient discriminatory power for risk assessment of HCO1 in aquatic environments. Based on the present results, more efficient risk assessment procedures for HCO1 will be designed in the future, integrating more flexible testing methods into the testing schemes that employ only the necessary tools for each case.
Animals↗
Survival of patchwork melanoblasts is dependent upon their number in the hair follicle at the end of embryogenesis.
The recessive patchwork (pwk) mutation in mice is associated with a unique hair follicle phenotype. Mice homozygous for patchwork exhibit a variegated coat containing a mixture of white and fully pigmented hairs, but no partially pigmented hairs. We have investigated the etiology of this mutation. We report here that the white hairs result from the lack of melanocytes in the follicle. As indicated by the coat color pattern of patchwork<-->albino chimeras, the target cell for the patchwork mutation is the melanocyte and/or its precursor. Examination of these chimeras also suggested that patchwork does not act in a cell-autonomous manner. The colonization of the skin by melanoblasts in patchwork embryos was studied using a lacZ transgene. Melanoblasts die by apoptosis in hair follicles from homozygous pwk/pwk fetuses starting at embryonic day 18.5, indicating that patchwork acts from this stage. The combination of pwk and KitW-ei, a mutation responsible for a reduced number of melanoblasts in the hair follicle, suggested that pwk gene product is necessary for low numbers of melanoblasts to survive and differentiate in the hair follicle from embryonic day 18.5 onward. We conclude that the pigmented hairs on the coat of pwk/pwk mice may be attributed to a community effect among melanoblasts in the hair follicle at the end of embryogenesis.
Animals↗
Obstructive cardiomyopathy in a male dwarf with cryptorchidism.
Obstructive cardiomyopathy has been reported in cases of male and female Turner phenotype with normal chromosomes. We report here a case of a male dwarf with bilateral undescended testes and biventricular obstructive cardiomyopathy. Clinical features included choreoathetoid movements, chorioretinitis, bilateral nystagmus, and unusual red color of the hair, associated with some features of Turner phenotype. Endocrine studies were normal except for a lack of thyrotrophic stimulating hormone (TSH) stimulation. Propranolol removed the gradient during cardiac catheterization and relieved the exertional chest pain clinically.
Adult↗
Functional analysis of the slaty gene product (TRP2) as dopachrome tautomerase and the effect of a point mutation on its catalytic function.
Slaty (slt), an autosomal recessive mutation that arose in YZ57/Ch mice, results in the dilution of coat color and premature hair loss. Recently, a gene encoding a homologue of the melanogenic enzyme tyrosinase (termed tyrosinase related protein 2 or TRP2) was cloned and was subsequently mapped to the slaty locus on chromosome 14. TRP2 was shown to function in melanogenesis as DOPAchrome tautomerase by means of the catalytic activity of the immunopurified protein and in slaty mutant skin samples. In this study, we generated an expression vector of a murine TRP2 encoding cDNA and are able to confirm its activity as DOPAchrome tautomerase. We further demonstrate that the slaty mutation dramatically decreases the catalytic function of the protein.
Animals↗
EMX homeobox genes regulate microphthalmia and alter melanocyte biology.
Melanocytes are specialized cells that produce melanin, the pigment responsible for skin, hair and retina color. They derive during embryogenesis from the precursor cells melanoblasts, which are neural crest cells committed to the pigment cell lineage. The differentiation of melanoblasts into melanocytes involves the expression of melanocyte-specific genes, particularly those responsible for melanin production, such as Tyr, Tyrp-1 and Dct, the expression of which depends on the melanocyte-specific transcription factor microphthalmia (Mitf). We have developed and executed a functional screen on melanocytes, with the aim of identifying genes involved in pigment cell biology. We have found Emx1 and Emx2, two highly related homeobox genes that when overexpressed in melanocytes can downregulate Mitf, Tyrp1, Dct and Tyr. Constitutive expression of Emx alters pigment cell morphology and growth properties: it confers TPA independence but not the ability to grow in soft agar. Spatial and temporal expression of Emx and Mitf during embryonic development suggests that Emx could be one factor that regulates correct expression of Mitf by inhibiting its activation in neuroepithelial derivatives other than melanocytes.
Animals↗
Modulatory effect of henna leaf (Lawsonia inermis) on drug metabolising phase I and phase II enzymes, antioxidant enzymes, lipid peroxidation and chemically induced skin and forestomach papillomagenesis in mice.
Henna leaf (Lawsonia inermis), commonly known as Mehndi is cultivated throughout India and is a very popular natural dye to color hand and hair. It is an integral part of indigenous culture, and is also known for its medicinal value. The effect of 200 and 400 mg/kg body weight of 80% ethanolic extract of the fresh leaves of Lawsonia inermis were examined on drug metabolizing phase-I and phase-II enzymes, antioxidant enzymes, glutathione content, lactate dehydrogenase and lipid peroxidation in the liver of 7 weeks old Swiss albino mice. Also anticarcinogenic potential of Henna leaf extract was studied adopting the protocol of benzo(a)pyrene induced forestomach and 7,12 dimethylbenz(a)anthracene (DMBA)-initiated and croton oil-promoted skin papillomagenesis. Our primary findings reveal the 'duel-acting' nature of henna leaf as deduced from its potential to induce only the phase-II enzyme activity, associated mainly with carcinogen detoxification in liver of mice and inhibit the phase I enzyme activities. The hepatic glutathione S-transferase and DT-diaphorase specific activities were elevated above basal (p < 0.005) level by Lawsonia inermis extract treatment. With reference to antioxidant enzymes the investigated doses were effective in increasing the hepatic glutathione reductase (GR), superoxide dismutase (SOD) and catalase activities significantly (from p < 0.05 to p < 0.005) at both the dose levels. Reduced glutathione (GSH) measured as non-protein sulphydryl was found to be significantly elevated in liver (p < 0.005) and in all the extrahepatic organs studied (from p < 0.05 to p < 0.005). Among the extrahepatic organs examined (forestomach, kidney and lung) glutathione S-transferase and DT-diaphorase level were increased in a dose independent manner (from p < 0.05 to p < 0.005). Chemopreventive response was measured by the average number of papillomas per mouse (tumor burden) as well as percentage of tumor bearing animals and tumor multiplicity. There was a significant inhibition of tumor burden in both the tumor model systems studied (from p < 0.01 to p < 0.001). Tumor incidence was also reduced by both the doses used in our experiment in both the model systems.
Animals↗
Oxyresveratrol and hydroxystilbene compounds. Inhibitory effect on tyrosinase and mechanism of action.
Tyrosinase is responsible for the molting process in insects, undesirable browning of fruits and vegetables, and coloring of skin, hair, and eyes in animals. To clarify the mechanism of the depigmenting property of hydroxystilbene compounds, inhibitory actions of oxyresveratrol and its analogs on tyrosinases from mushroom and murine melanoma B-16 have been elucidated in this study. Oxyresveratrol showed potent inhibitory effect with an IC(50) value of 1.2 microm on mushroom tyrosinase activity, which was 32-fold stronger inhibition than kojic acid, a depigmenting agent used as the cosmetic material with skin-whitening effect and the medical agent for hyperpigmentation disorders. Hydroxystilbene compounds of resveratrol, 3,5-dihydroxy-4'-methoxystilbene, and rhapontigenin also showed more than 50% inhibition at 100 microm on mushroom tyrosinase activity, but other methylated or glycosylated hydroxystilbenes of 3,4'-dimethoxy-5-hydroxystilbene, trimethylresveratrol, piceid, and rhaponticin did not inhibit significantly. None of the hydroxystilbene compounds except oxyresveratrol exhibited more than 50% inhibition at 100 microm on l-tyrosine oxidation by murine tyrosinase activity; oxyresveratrol showed an IC(50) value of 52.7 microm on the enzyme activity. The kinetics and mechanism for inhibition of mushroom tyrosinase exhibited the reversibility of oxyresveratrol as a noncompetitive inhibitor with l-tyrosine as the substrate. The interaction between oxyresveratrol and tyrosinase exhibited a high affinity reflected in a K(i) value of 3.2-4.2 x 10(-7) m. Oxyresveratrol did not affect the promoter activity of the tyrosinase gene in murine melanoma B-16 at 10 and 100 microm. Therefore, the depigmenting effect of oxyresveratrol works through reversible inhibition of tyrosinase activity rather than suppression of the expression and synthesis of the enzyme. The number and position of hydroxy substituents seem to play an important role in the inhibitory effects of hydroxystilbene compounds on tyrosinase activity.
Agaricales↗
Final report of the safety assessment of L-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate as used in cosmetics.
L-Ascorbic Acid, Calcium Ascorbate, Magnesium Ascorbate, Magnesium Ascorbyl Phosphate, Sodium Ascorbate, and Sodium Ascorbyl Phosphate function in cosmetic formulations primarily as antioxidants. Ascorbic Acid is commonly called Vitamin C. Ascorbic Acid is used as an antioxidant and pH adjuster in a large variety of cosmetic formulations, over 3/4 of which were hair dyes and colors at concentrations between 0.3% and 0.6%. For other uses, the reported concentrations were either very low (<0.01%) or in the 5% to 10% range. Calcium Ascorbate and Magnesium Ascorbate are described as antioxidants and skin conditioning agents--miscellaneous for use in cosmetics, but are not currently used. Sodium Ascorbyl Phosphate functions as an antioxidant in cosmetic products and is used at concentrations ranging from 0.01% to 3%. Magnesium Ascorbyl Phosphate functions as an antioxidant in cosmetics and was reported being used at concentrations from 0.001% to 3%. Sodium Ascorbate also functions as an antioxidant in cosmetics at concentrations from 0.0003% to 0.3%. Related ingredients (Ascorbyl Palmitate, Ascorbyl Dipalmitate, Ascorbyl Stearate, Erythorbic Acid, and Sodium Erythorbate) have been previously reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel and found "to be safe for use as cosmetic ingredients in the present practices of good use." Ascorbic Acid is a generally recognized as safe (GRAS) substance for use as a chemical preservative in foods and as a nutrient and/or dietary supplement. Calcium Ascorbate and Sodium Ascorbate are listed as GRAS substances for use as chemical preservatives. L-Ascorbic Acid is readily and reversibly oxidized to L-dehydroascorbic acid and both forms exist in equilibrium in the body. Permeation rates of Ascorbic Acid through whole and stripped mouse skin were 3.43 +/- 0.74 microg/cm(2)/h and 33.2 +/- 5.2 microg/cm(2)/h. Acute oral and parenteral studies in mice, rats, rabbits, guinea pigs, dogs, and cats demonstrated little toxicity. Ascorbic Acid and Sodium Ascorbate acted as a nitrosation inhibitor in several food and cosmetic product studies. No compound-related clinical signs or gross or microscopic pathological effects were observed in either mice, rats, or guinea pigs in short-term studies. Male guinea pigs fed a control basal diet and given up to 250 mg Ascorbic Acid orally for 20 weeks had similar hemoglobin, blood glucose, serum iron, liver iron, and liver glycogen levels compared to control values. Male and female F344/N rats and B6C3F(1) mice were fed diets containing up to 100,000 ppm Ascorbic Acid for 13 weeks with little toxicity. Chronic Ascorbic Acid feeding studies showed toxic effects at dosages above 25 mg/kg body weight (bw) in rats and guinea pigs. Groups of male and female rats given daily doses up to 2000 mg/kg bw Ascorbic Acid for 2 years had no macro- or microscopically detectable toxic lesions. Mice given Ascorbic Acid subcutaneous and intravenous daily doses (500 to 1000 mg/kg bw) for 7 days had no changes in appetite, weight gain, and general behavior; and histological examination of various organs showed no changes. Ascorbic Acid was a photoprotectant when applied to mice and pig skin before exposure to ultraviolet (UV) radiation. The inhibition of UV-induced suppression of contact hypersensitivity was also noted. Magnesium Ascorbyl Phosphate administration immediately after exposure in hairless mice significantly delayed skin tumor formation and hyperplasia induced by chronic exposure to UV radiation. Pregnant mice and rats were given daily oral doses of Ascorbic Acid up to 1000 mg/kg bw with no indications of adult-toxic, teratogenic, or fetotoxic effects. Ascorbic Acid and Sodium Ascorbate were not genotoxic in several bacterial and mammalian test systems, consistent with the antioxidant properties of these chemicals. In the presence of certain enzyme systems or metal ions, evidence of genotoxicity was seen. The National Toxicology Program (NTP) conducted a 2-year oral carcinogenesis bioassay of Ascorbic Acid (25,000 and 50,000 ppm) in F344/N rats and B6C3F(1) mice. Ascorbic Acid was not carcinogenic in either sex of both rats and mice. Inhibition of carcinogenesis and tumor growth related to Ascorbic Acid's antioxidant properties has been reported. Sodium Ascorbate has been shown to promote the development of urinary carcinomas in two-stage carcinogenesis studies. Dermal application of Ascorbic Acid to patients with radiation dermatitis and burn victims had no adverse effects. Ascorbic Acid was a photoprotectant in clinical human UV studies at doses well above the minimal erythema dose (MED). An opaque cream containing 5% Ascorbic Acid did not induce dermal sensitization in 103 human subjects. A product containing 10% Ascorbic Acid was nonirritant in a 4-day minicumulative patch assay on human skin and a facial treatment containing 10% Ascorbic Acid was not a contact sensitizer in a maximization assay on 26 humans. Because of the structural and functional similarities of these ingredients, the Panel believes that the data on one ingredient can be extrapolated to all of them. The Expert Panel attributed the finding that Ascorbic Acid was genotoxic in these few assay systems due to the presence of other chemicals, e.g., metals, or certain enzyme systems, which effectively convert Ascorbic Acid's antioxidant action to that of a pro-oxidant. When Ascorbic Acid acts as an antioxidant, the Panel concluded that Ascorbic Acid is not genotoxic. Supporting this view were the carcinogenicity studies conducted by the NTP, which demonstrated no evidence of carcinogenicity. Ascorbic Acid was found to effectively inhibit nitrosamine yield in several test systems. The Panel did review studies in which Sodium Ascorbate acted as a tumor promoter in animals. These results were considered to be related to the concentration of sodium ions and the pH of urine in the test animals. Similar effects were seen with sodium bicarbonate. Because of the concern that certain metal ions may combine with these ingredients to produce pro-oxidant activity, the Panel cautioned formulators to be certain that these ingredients are acting as antioxidants in cosmetic formulations. The Panel believed that the clinical experience in which Ascorbic Acid was used on damaged skin with no adverse effects and the repeat-insult patch test (RIPT) using 5% Ascorbic Acid with negative results supports the finding that this group of ingredients does not present a risk of skin sensitization. These data coupled with an absence of reports in the clinical literature of Ascorbic Acid sensitization strongly support the safety of these ingredients.
Administration, Oral↗
Letter: Mutagenicity of commercially available hair dyes. What significance for humans?
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Coloring Agents↗
Cross-sectional study of recurrent herpes labialis. Prevalence and risk factors.
Consecutive blood donors at 25 sites in southern Wisconsin were interviewed in 1985 to ascertain recurrent herpes labialis histories, other perioral conditions, and status on possible predisposing factors and correlates of lesion recurrence. The prevalence of recurrent herpes labialis was 32.9%. Of the cases, 51.3% reported at least two recurrences per year, 8.6% characterized their condition as severe, and 10% sought medical care. Relations were examined between recurrent herpes labialis and family history of the disease, ethnicity, complexion, hair and eye color, other chronic perioral conditions, solar radiation, exposure to dental procedures, and smoking. The risk of recurrent herpes labialis associated with disease in various first-degree family members, estimated by age-adjusted odds ratios (nominal 95% confidence intervals) were: mother, 3.30 (1.86-5.84); father, 3.80 (1.80-8.12); sister(s), 3.93 (2.25-6.89); and brother(s), 6.81 (3.14-15.04). Ethnicity and phenotypes were not related to disease status. Cases had a higher prevalence of recurrent aphthous ulcers (odds ratio = 3.00, 95% confidence interval = 1.79-5.02) and reported more exposure to solar radiation and more extensive dental histories.
Adolescent↗
Solar ultraviolet radiation exposure does not appear to exacerbate HIV infection in homosexual men. The Multicenter AIDS Cohort Study.
OBJECTIVE: To determine the effect of sun exposure on HIV progression. DESIGN: Cross-sectional survey nested within a longitudinal cohort study. SETTING: The Multicenter AIDS Cohort Study. PARTICIPANTS: A total of 1155 white HIV-seronegative and 496 white HIV-seropositive homosexual men, of whom 142 seroconverted during the study. MAIN OUTCOME MEASURES: T-helper lymphocyte decline and AIDS. RESULTS: No positive correlation was found between the development of AIDS or loss of T-helper lymphocytes and (i) phenotypic characteristics associated with enhanced ultraviolet radiation (UVR) sensitivity (hair or eye color, skin type), or (ii) reported UVR exposure (sun lamp/tanning bed use, frequency of beach vacations, sunscreen use), or (iii) composite score of UVR sensitivity and exposure history. The composite scores and individual measures of risk were not correlated with rate of T-helper lymphocyte decline (slope) based upon rank correlation (correlation coefficient, 0.04; P = 0.32). In fact, individuals purposefully seeking the sun had slower T-helper lymphocyte declines. Sensitivity to UVR was also not significantly associated with AIDS [odds ratio (OR), 1.11 per unit of higher composite score; 95% confidence interval (CI), 0.66-1.88; P = 0.63]. Among individuals who were HIV-infected at baseline, those who have been purposely seeking sun exposure were less likely to have AIDS (OR, 0.67; 95% CI, 0.39-1.11; P = 0.12). CONCLUSIONS: These data suggest that phenotypic characteristics of high UVR sensitivity and exposure are not highly correlated with decline in T-helper lymphocyte count or with progression to AIDS.
Adult↗
Recent advances in the chemistry of melanogenesis in mammals.
The color of mammalian hair, skin, and eyes results mainly from the secretory products of melanocytes. These secretory products consist of a wide range of melanin pigments with different structures and compositions. These include black or brown nitrogenous eumelanins; yellow or reddish brown, sulfur-containing pheomelanins, e.g., the trichochromes of low molecular weight; and other pigments whose chemical and physical properties are intermediate between those of typical eumelanins and pheomelanins. Despite the evident differences in molecular size and general properties, all these pigments are biogenetically related, and they arise from a common mmetabolic pathway in which dopaquinone is the key intermediate. The current state of knowledge on the molecular mechanisms governing the etabolic fate of dopaquinone in melanocytes is discussed with special reference to the role of such sulfhydryl compounds as cysteine and glutathione in melanogenesis.
Animals↗
Ultraviolet carcinogenesis in nonmelanoma skin cancer part II: review and update on epidemiologic correlations.
The relationship between ultraviolet radiation and nonmelanoma skin cancer (NMSC) is further elucidated by a review of case-control studies relating type of exposure to the development of NMSC. Intermittent sun exposure is important in the pathogenesis of basal cell carcinoma, whereas cumulative exposure is important for both basal cell carcinoma and squamous cell carcinoma. The regional distribution of NMSC is also in areas of sun exposure. Furthermore, there are inherent risk factors for the development of NMSC that include hair and eye colors. Once an individual develops NMSC, he/she has increased risk of developing basal cell carcinoma, squamous cell carcinoma, or melanoma.
Basal Cell Carcinoma↗
The interaction of agouti signal protein and melanocyte stimulating hormone to regulate melanin formation in mammals.
Important regulatory controls of melanogenesis that operate at the subcellular level to modulate the structural and/or the functional nature of the melanins and melanin granules produced in melanocytes are reviewed. Melanocyte stimulating hormone and agouti signal protein have antagonistic roles and possibly opposing mechanisms of action in the melanocyte. In the mouse, melanocyte stimulating hormone promotes melanogenic enzyme function and elicits increases in the amount of eumelanins produced, while agouti signal protein reduces total melanin production and elicits the synthesis of pheomelanin rather than eumelanin. We are now beginning to understand the complex controls involved in regulating this switch at the molecular and biochemical levels. The quality and quantity of melanins produced by melanocytes have important physiological consequences for melanocyte function and undoubtedly play important roles in the various functions of the melanins per se, including hair and skin coloration and photoprotection.
Agouti Signaling Protein↗
Population differences in the frequency of the agouti signaling protein g.8818a>G polymorphism.
The role of agouti signaling protein (ASIP) in human pigmentation pathways is not definitively understood although its murine homologue regulates, in part, pheomelanogenesis. We have reported an association of a polymorphism in the 3'-untranslated region of ASIP (g.8818A>G) with dark hair and eye color among a group of European-Americans (Am J Hum Genet 2002 March;70:770). Among 147 healthy control subjects, the frequency of the G-allele was 0.12. We hypothesized that this polymorphism would occur at different frequencies among different population groups. Using PCR-RFLP, we genotyped 25 East Asian, 86 African-American, and 207 West African individuals for the ASIP g.8818A>G polymorphism. The g.8818G-allele was present in the West African sample at a frequency of 0.80, in the African-American sample at a frequency of 0.62, and in the East Asian sample at 0.28. The difference in allele frequency among population groups was statistically significant (P < 0.0001). Although the effect of the g.8818A>G polymorphism upon ASIP function is unknown, the large difference in allele frequency between our West African and European-American sample populations lends support to the notion that this gene may be important in human pigmentation.
Agouti Signaling Protein↗
AGOUTI LOCUS: HOMOLOGY OF ITS METHOD OF OPERATION IN RATS AND MICE.
The action of genes at the agouti locus in rats is similar to that of genes at the same locus in mice-the color phenotype of hairs is determined by the operation of agouti-locus alleles in the follicle, rather than in the melanocytes. Hairs produced by mouse skin growing on partially tolerant infant rat hosts show that rat melanocytes also respond to the agouti-locus genotype of mouse follicles. This constitutes the first example in vivo of the behavior of a cell of one species being completely determined by the genotype of an alien host species.
Alleles↗
Positive and negative elements regulate a melanocyte-specific promoter.
Melanocytes are specialized cells residing in the hair follicles, the eye, and the basal layer of the human epidermis whose primary function is the production of the pigment melanin, giving rise to skin, hair, and eye color. Melanogenesis, a process unique to melanocytes that involves the processing of tyrosine by a number of melanocyte-specific enzymes, including tyrosinase and tyrosinase-related protein 1 (TRP-1), occurs only after differentiation from the melanocyte precursor, the melanoblast. In humans, melanogenesis is inducible by UV irradiation, with melanin being transferred from the melanocyte in the epidermis to the surrounding keratinocytes as protection from UV-induced damage. Excessive exposure to UV, however, is the primary cause of malignant melanoma, an increasingly common and highly aggressive disease. As an initial approach to understanding the regulation of melanocyte differentiation and melanocyte-specific transcription, we have isolated the gene encoding TRP-1 and examined the cis- and trans-acting factors required for cell-type-specific expression. We find that the TRP-1 promoter comprises both positive and negative regulatory elements which confer efficient expression in a TRP-1-expressing, pigmented melanoma cell line but not in NIH 3T3 or JEG3 cells and that a minimal promoter extending between -44 and +107 is sufficient for cell-type-specific expression. Assays for DNA-protein interactions coupled with extensive mutagenesis identified three factors, whose binding correlated with the function of two positive and one negative regulatory element. One of these factors, termed M-box-binding factor 1, binds to an 11-bp motif, the M box, which acts as a positive regulatory element both in TRP-1-expressing and -nonexpressing cell lines, despite being entirely conserved between the melanocyte-specific tyrosinase and TRP-1 promoters. The possible mechanisms underlying melanocyte-specific gene expression are discussed.
Amino Acid Sequence↗