摘要:

The rationale for melanoma specific dihydroxybenzene containing antitumor agents is based in part upon the ability of the enzyme tyrosinase to oxidize these pro drugs to toxic intermediates. In situ tyrosinase activity was demonstrated to be affected by both cell density and time from plating in pigmented melanoma cells. Phenylthiourea, which completely inhibited tyrosinase activity with minimal cytotoxicity was found to block the growth inhibitory activity of the antitumor dopamine analog 3,4‐dihydroxybenzylamine (3,4‐DHBA) (NSC 263475). The antioxidant dithioerythritol was also found to inhibit tyrosinase activity and to block the growth inhibitory effects of 3,4‐DHBA in pigmented melanoma cell lines. Buthionine sulfoximine (BSO) was shown to be cytotoxic to melanoma cells and its growth inhibitory effects appears to correlate with tyrosinase levels. Furthermore, BSO was shown to potentiate the growth inhibitory effects of 3,4‐DHBA on marginally pigmented human melanoma cel

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1990.tb00322.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Normal adult human melanocytes grown either in the presence of phorbol ester or dialyzed hypothalamic extract were analyzed for their cell surface sialic acid and galactose content. In both cases, cells expressed large amounts of sialic acid, whereas they differed in their terminal nonreducing β‐D‐galactosyl residues linked to N‐acetyl galactosamine; such residues were accessible to peanut agglutinin andBauhinia purpurealectin on cells grown in phorbol ester and inaccessible on cells grown with dialyzed hypothalamic extract. In addition, striking differences in morphology and growth characteristics were observed between adult melanocytes grown with phorbol ester or with dialyzed hypothalamic extract. Thus, pure cultures of normal adult human melanocytes grown in the presence of dialyzed hypothalamic extract displayed cell surface properties different from those of melanocytes grown with phorbol ester. Cultures of melanocytes with dialyzed hypothalamic extract are likely to reflect known cell surface characteristics of human melanocytes in the skin. Such cultures could represent a useful model to study normal behavior and tumor progression of pigmented

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1990.tb00323.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The distribution of GTP‐cyclohydrolase I, pyruvoyl tetrahydropterin (dysopropterin) synthase, and pyruvoyl tetrahydropterin reductase in goldfish erythrophores, melanophores, and erythrophoroma cells in vitro has been revealed by specific biochemical assays. The activity of pyruvoyl tetrahydropterin synthase in the erythrophores is nearly the same as that in rat kidney and pineal gland. Results of the simultaneous quantification of unconjugated pteridines (biopterin, sepiapterin, neopterin, and pterin) by HPLC indicate that the total amounts of these derivatives present in these cells and in the respective culture media are closely correlated with the activities of these enzymes. These findings imply that these cells are capable of the autonomous synthesis of pteridines, which most likely proceeds from GTP to 6‐lactoyl‐5,6,7,8‐tetrahydropterin (reduced sepiapterin), via dihydroneopterin triphosphate and pyruvoyl tetrahydropterin, through reactions catalyzed by these enzymes. A comparison of pteridine metabolism between clones of the stem cell type and the yellow‐pigmented clones induced from erythrophoroma cells suggests that brightly colored pigmentation involves two separate phases: the biosynthesis of pteridines and their deposition in the pigment organelles. The presence of the highly active pteridine‐synthesizing enzymes in melanophores and melanogenic erythrophoroma cells strongly suggests a loose commitment to the expression of pigment phenotypes in t

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1990.tb00324.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Topical applications of monobenzylether of hydroquinone (MBEH) or intraperitoneal injections of phenol induced graying of hair in eumelanic mice but had little effect on hair color in pheomelanic mice. Amcinonide, an anti‐inflammatory agent, elicited whitening of a few hairs in both pheomelanic and eumelanic mice. In phenol‐treated eumelanic mice, damaged follicular melanocytes were uprooted from hair bulbs and incorporated into the developing hair. The fate of follicular melanocytes in MBEH‐ or amcinonide‐treated mice was not determined since hair growth and graying were more variable than in phenol‐treated mice.In contrast to the susceptibility of eumelanic hair follicles to depigmentation by phenol or MBEH, the tail skin of eumelanic or pheomelanic mice was not depigmented by these agents. Overall, during the 3 week period of treatment that was sufficient for phenol or MBEH to elicit graying of hair, epidermal melanocytes of the tails of eumelanic or pheomelanic mice either failed to respond (phenol) or were stimulated in their “proliferative” and melanogenic activity (MBEH). In contrast, amcinonide brought about a marked reduction in the numbers of DOPA‐positive epidermal melanocytes inhabiting the tails of eumelanic or pheomelanic mice. Amcinonide exerted a deleterious influence on the structure and function of tail epidermis. Its actions were partly reversed by simultaneous treatment with MBEH but not with prost

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1990.tb00325.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The pigmentary system of skin from adult specimens of the amphibian urodeleSalamandra atra auroraewas investigated by light microscope, electron microscope, and biochemical studies. Yellow (dorsum and head) and black (flank and belly) skin was tested.Three chromatophore types are present in yellow skin: xanthophores, iridophores, and melanophores. Xanthophores are located in the epidermis whereas iridophores and melanophores are found in the dermis. Xanthophores contain types I, II, and III pterinosomes. Some pterinosomes are very electron‐dense.Black skin has a single type of chromatophore: the melanophores. Some melanophores are located in the epidermis. In contrast to the dermal melanophores, these present, in addition to typical melanosomes, organelles with different morphology and vesicles having a limiting membrane and containing little amorphous material.Both skin types present some pteridines and flavins, though they are qualitatively and quantitatively more abundant in yellow skin extract

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1990.tb00326.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Although pigment melanin has long been thought of as “inert,” recent work has attested to its chemical reactivity. In this communication, we report that either commercial synthetic melanin prepared by persulfate oxidation of tyrosine (“Sigma melanin”) or sepia melanin extracted from cuttlefish markedly accelerates the in vitro oxygenation of p‐hydroxyanisole (MMEH), catalyzed by mushroom or B‐16 melanoma tyrosinase. Kinetics of 4‐methoxy‐1,2‐benzoquinone formation (λmax = 413 nm) or of molecular O2uptake were biphasic, with an initial slow rate (“lag time”) followed by a fast linear increase. The biphasic response reflects an initial slow hydroxylation followed by a fast dehydrogenation. Added melanin markedly decreased the lag time but had little effect on subsequent dehydrogenation. Similar effects were observed for tyrosine itself. A complex between MMEH and melanin appears to be the “active” species in these reactions. The results indicate that melanin acts as an electron conduit, which accepts electrons from the substrate and transfers them to tyrosinase. The magnitude of the effect depends on the type of melanin as well as on its oxidation state. Kinetic analysis indicates that both melanins are very efficient at transferring electron to tyrosinase, and that Sigma melanin is roughly threefold more efficient than sepia melanin. The qualitative similarity of reaction between the synthetic and “natural” melanins suggests that the former may serve as a first approximation to the in vivo situation. On the other hand, the observed quantitative differences and the sensitivity of these results to the chemical state of melanin suggests that this methodology might eventually be adapted as a non‐destructive probe of melanin in situ. These results also hint at a “dark side,” of melanin, through which cytotoxic

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1990.tb00327.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Sapintoxin A (SAP A), a naturally occurring biologically active but non‐promoting phorbol ester, acts as an effective in vitro mitogen for freshly derived human melanocytes. Seven days after addition of 50 nM SAP A there was a four to fivefold increase in melanocyte number over that observed in untreated control cultures comparable to that achieved with a 50 nM concentration of 12‐0‐tetradecanoylphorbol 13‐acetate (TPA). The fluorescent stage 2 promoter sapintoxin D (SAP D) also supported the growth of these cells, with a 50 nM dose producing an increase in cell number comparable to that observed with 200 nM TPA. Similar results were obtained with an established, but non‐tumorigenic, line of murine melanocytes. The same compounds exerted a potent anti‐proliferative effect against transformed melanocyte lines of murine and human origin associated with morphological alterations and an increase in melanin production consistent with induced cytodiff

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1990.tb00328.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

We have studied the development ofXenopus laevistail melanophores and the effects on these cells on confrontation with endogenousX. laevisgalactoside‐binding lectin or its sugar hapten inhibitor thiodigalactoside (TDG). An initial population of unpigmented cells differentiates into melanophores on the dorsal surface of the neural tube, and on the dorsal and ventral apices of the myotomes, forming the larval pattern. Melanophores secondarily populate the flank, forming a spaced arrangement which is later transformed into a dorsal and ventral stripe. A technique has been developed for confrontation of premigratory neural crest with purified lectin or TDG. These molecules impact on tail melanophores. With lectin treatment melanophore numbers decrease, and cell morphologies and arrangements change. TDG treatment, however, primarily affects pigment cell morphology. These results suggest that both galactoside‐bearing receptors for this lectin and the lectin itself can affect melanophores in this species of f

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1990.tb00329.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The protective role of melanin as an antioxidant biopolymer against lipid peroxidation was investigated. In pigmented frog liver and in albino rat liver the following were tested: thiobarbituric acid (TBA) reactive material (to show the induced lipoperoxidation in vitro), fatty acids, and reduced glutathione content. Our results show that susceptibility to the in vitro lipoperoxidation induced by ferrous ions is lower in the tissue containing melanin, though the content of the polyunsaturated fatty acids is higher in pigmented than in unpigmented tissues and reduced glutathione levels are lower in pigmented tissue. Our data support the hypothesis that melanin could reduce lipoperoxidation in pigmented tissue.

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1990.tb00330.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

The melanin content ofRana esculentaL. liver varies according to a circannual statistically significant rhythm, as shown by variance and single cosinor analysis. The maximum is found in autumn‐winter, the minimum in spring‐summer. The linear regression analysis shows a negative correlation between the amount of melanin and the environmental temperat

ISSN:0893-5785    

DOI:10.1111/j.1600-0749.1990.tb00331.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY