Absence Of Melanin Research Articles

Ultrastructural changes produced in Ehrlich ascites carcinoma cells by ultraviolet-visible radiation in the presence of melanins.

Irradiation of Ehrlich ascites carcinoma (EAC) cells in the presence of pheomelanin, i.e., red hair melanin (RHM), has been reported to produce extensive cell lysis. Irradiation in the presence of eumelanin, i.e., black hair melanin (BHM), or irradiation in the absence of either type of melanin did not produce this effect. We observed that RHM particles penetrated the cell membrane without apparent structural damage to the cell or the cell membrane. Irradiation of the cells in the absence of melanin did not produce any changes in the ultrastructure of the cells. Incubation of the cells in the dark in the presence of RHM produced only minor structural, mainly cytoplasmic changes. Irradiation of the cells in the presence of RHM produced extensive ultrastructural changes prior to complete cell lysis; these changes were more severe than the effects of incubation of the cells in the dark in the presence of RHM. When the cells incubated in the dark or irradiated in the presence of latex particles or either one of the eumelanins particles, viz. BHM or synthetic dopa melanin, these particles did not penetrate into the cells or produce any ultrastructural changes. These particles were in fact not even ingested by the cells.

Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on dopamine synthesis and release in the rabbit retina in vitro

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the synthesis and release of dopamine (DA) was investigated in the retina of the rabbit in vitro. The results indicated that MPTP did not affect the synthesis of DA, but increased its release. Blockade of the activity of monoamine oxidase (MAO) with pargyline (100 μM) did not abolish the capacity of MPTP to release DA. Similarly, these pharmacological effects of MPTP were not dependent on the presence or absence of melanin.

Genetic and developmental studies of albino chorus frogs

Albino (amelanic) adult chorus frogs (Pseudacris triseriata) occurred with frequencies of 7 percent in 1981 and 12 percent in 1982 in breeding aggregations at a pond in the foothills of the Colorado Front Range. Laboratory matings and examination of albino egg masses suggest that the absence of melanin is due to a recessive allele. The albino phenotype displayed no deficiencies in survival of embryos, rates of embryo or larval development, or rates of growth of juvenile frogs. The absence of abnormalities in development or growth suggests that the a allele in P. triseriata has an action different from albino alleles studied previously in anurans.

Interaction of several mono- and dihydroxybenzene derivatives of various depigmenting potencies with l-3,4-dihydroxyphenylalanine-melanin

Certain mono- and dihydroxybenzene derivatives cause depigmentation of skin and hair, and appear to be selectively cytotoxic for melanized pigment cells. As direct physical and/or chemical interaction between depigmenter (DP) and pigment melanin may play a role in depigmentation, we have carried out preliminary studies in model systems where such interactions may easily be separated from effects due to tyrosinase, melanosomal proteins, and other components. We have used synthetic l-3,4-hydroxyphenylalanine ( l-DOPA)-melanin as a protein-free model pigment and potassium ferricyanide as a model electron acceptor. Compounds studied were catechol, 4-t-butylcatechol, 4-methylcatechol, 3,4-dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylacetic acid, hydroquinone, 4-methoxyphenol, 4-t-butylphenol, and 2,6, di-t-butyl-4-methylphenol (BHT) in 0.1 M phosphate buffer, pH 7.4. These compounds vary widely in their ability to depigment hair and skin. Ferricyanide reduction by DP in the presence and absence of melanin was monitored spectrophotometrically. The sparingly soluble BHT and 4-t-butylphenol did not reduce ferricyanide in the absence or presence of melanin. For the other compounds, kinetic analysis demonstrated direct interaction between each DP and melanin. Except for dihydroxyphenylacetic acid, reduction kinetics were consistent with a mechanism involving noninteractive binding of both DP and ferricyanide to melanin prior to coupled electron transfer through the melanin backbone. Kinetic analysis afforded K B, a thermodynamic constant (M −1) for DP-melanin binding, and k′, a rate parameter (M s −1) for electron transfer. A dimensionless enhancement factor (EF) was defined as k′K B k s , with k s a pseudo-first-order constant (s −1) for ferricyanide reduction in the absence of melanin. Depending on the reductant, melanin either retards (EF < 1) or accelerates (EF > 1) the rate of ferricyanide reduction. There appears to be a direct relationship between EF and depigmenting potency. There is no relationship between depigmenting power and the ability per se of the DP to bind to melanin or to reduce ferricyanide.

Histochemical observations on rodent brain melanin

The presence or absence of melanin and neuromelanin in rodent brain was determined by means of light microscopic histochemistry. Melanin in melanocytes located in meninges and along cerebral capillaries occurred in abundance in C57 black mice and to a lesser extent in pigmented rats. Meningeal melanin bound cupric and ferrous ions, reduced ferricyanide, and appeared golden-brown in the bright field, light scattering in the dark field, and absorbant in the ultraviolet. Eleven aging albino rats were utilized to ascertain if the age related pigment, neuromelanin was present in neurons of the substantia nigra. Evidence of neuromelanin was not obtained as the cupric and ferrous ion uptake reactions were negative and neuromelanin could not be seen in the bright or dark field. Substantia nigra neurons did exhibit histochemical reactions for lipofuscin, however, as acid phosphatase positive, periodic acid-Schiff positive, and autofluorescent granules were demonstrated.

The Interaction of L-DOPA Melanin with p-tert-Butylcatechol

The interaction between the skin depigmenter 4-tert-butylcatechol (tBC) and L-DOPA melanin was qualitatively studied by means of spectroscopically monitoring the binding of tBC melanin as well as the oxidation of tBC in the presence and absence of melanin. Additionally, we assessed the quantitative effect of tBC on melanin's chemical reactivity by using the reduction of potassium ferricyanide as a redox marker. The kinetics of ferricyanide reduction in the ternary (melanin/tBC/ferricyanide) system are essentially different from those in each of the binary components (i.e., melanin/ferricyanide and tBC/ferricyanide). The experiments indicate that tBC can bind to melanin (KB = 3.8 X 10(3) M-1) and that melanin can act as a "catalyst-like" electron transfer agent which couples ferricyanide reduction with tBC oxidation (k' = 1.3 X 10(-6) mole min-1). These kinetic and thermodynamic parameters may provide a means of quantitatively comparing melanins obtained from different biological and pathological situations, and they may make possible an understanding of cutaneous depigmentation processes on the molecular level.

On the Nature and Excretion of the Hepatic Pigment in the Dubin-Johnson Syndrome

A dark hepatic pigment occurs in the Dubin-Johnson Syndrome (DJS) and it has been suggested but not proved that it is melanin. if acute viral hepatitis (AVH) complicates DJS, the pigment disappears from the liver and reappears after recovery. The unusually dark urine seen in a DJS patient with AVH suggested urine as the possible site of pigment excretion. We have used a sensitive new method for detecting melanin to investigate these problems. The method is based on the fact that melanin is an unusually stable free radical whose electron spin resonance (ESR) spectrum is characteristically altered by visible light, pH changes, zinc(II) and paramagnetic trace elements. Liver and urine specimens were examined in (a) a DJS patient during and after AVH, (b) patients with uncomplicated DJS, (c) patients with AVH without DJS, (d) patients with other types of hepatitis, and (e) patients with apparently normal livers. The ESR spectra indicated the absence of melanin in all specimens. A stable free radical with unusual properties was found in the liver of patients with uncomplicated DJS. This was absent from the liver of a DJS patient studied during acute hepatitis but was present in his urine. It disappeared from his urine during and after recovery from hepatitis. We conclude that the hepatic pigment in DJS is: (a) not melanin; (b) excreted in the urine during acute hepatitis; (c) a stable free radical; and (d) not present in the liver or urine in any of the other diseases that were studied.

Evaluation of prognosis in Stage I cutaneous melanoma.

A review of the literature on melanoma indicates that age, sex, size, ulceration, presence of satellites, absence of melanin, and whether or not the tumor is markedly raised above the surface of the surrounding skin are all useful criteria in evaluating the prognosis in Stage I cutaneous melanoma. Histological factors include the tumor type, the mitotic rate, and the maximum thickness of the tumor. The last is accurate for prognosis--objective, reproducible, and directly proportional to the mortality rate. Tumors less than 0.76 mm thick rarely, if ever, metastasize--and it appears that the size of the resection margin can safely be reduced for such thin tumors. The level of invasion (Clark) is less accurate in predicting the mortality.

Guttate Leukoderma in Darier's Disease

Widespread guttate leukoderma associated with keratosis follicularis occurred in three patients. These lesions were not preceded by inflammatory lesions and were usually found in areas free of the greasy papules of keratosis follicularis. The white macules show virtual absence of melanin on histological examination. We believe that the association of guttate leukoderma with keratosis follicularis is more common than the scant attention in the literature would indicate.

The biochemical effects of the d, m, and a genes on pigment cell differentiation in the axolotl

Summary Three mutations alter the basic pigmentation of the wild-type axolotl. In this study an attempt has been made to describe the biochemical alterations associated with these mutations and to correlate them with the cellular changes observed by other investigators and verified by this author. The a gene has no effect on either pteridine or purine synthesis or on xanthophore or iridiophore differentiation. Rather, it inactivates tyrosinase completely, resulting in the absence of melanin in albino axolotls. The effects of the m gene are primarily on the production of propigment cells by the neural crest. Transplants indicate that more melanophores and fewer xanthophores (than in the wild-type), and no iridiophores are produced in axolotls homozygous for m. Correlated with these observations are a 35% increase in tyrosinase activity and a 40% decrease in pteridine synthesis in melanoid animals. The former may, in part, be due to an increased amount of tyrosinase in each melanophore. Moreover, an accumulation of IDP + ITP, AMP, and an unidentified purine derivative suggest that a somewhat “leaky” enzymatic block in the conversion of IMP into XMP (or of XMP into GMP) may contribute to the reduction and absence, respectively, of fully differentiated xanthophores and iridiophores in melanoid skin. The extent of these contributions remains to be determined. Transplantation experiments indicate that the d gene does not alter the production of propigment cells by the neural crest. The 70% decrease in melanin synthesis (and melanophores) in white axolotls appears to be the result of decreased tyrosinase activity rather than of inhibited melanoblast migration. Likewise, the 50% decrease in pteridine synthesis (and xanthophores) appears to be the result of both decreased (40%) glucose-6-phosphate dehydrogenase activity during embryonic stages and of a “leaky” enzymatic block in the conversion of GMP into biopterin, rather than a result of inhibited xanthoblast migration. Since the former block is operative only during embryonic stages, and since the latter block results in a shunting of GMP into guanine synthesis, normal iridiophore differentiation occurs in axolotls homozygous for d.

Induction of Melanin Patterns and of Hardening as Separate Processes in the Cuticle of Albino Locusts with Internally Absorbed Phenol Substrates

THE cuticle of the albino strain of Schistocerca gregaria is more or less colourless because of a complete absence of melanin and apparent utilization of a phenol substrate in the hardening process which does not give rise to a coloured scleroprotein.