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Biomedical subjects

I A Menon

Publications and source records attributed to I A Menon.

At least 55 records · Page 3Linked to original sources

Effects of ultraviolet-visible irradiation in the presence of melanin isolated from human black or red hair upon Ehrlich ascites carcinoma cells.

The present study is an attempt to investigate the possibility that ultraviolet irradiation in the presence of pheomelanin may be more harmful to cells than the irradiation in the presence of eumelanin. The effects of UV-visible irradiation upon Ehrlich ascites carcinoma cells in the presence of the melanin isolated from human black hair (eumelanin) or from red hair (pheomelanin) were investigated. Irradiation of these cells was found to produce cell lysis, as observed by leakage of 51Cr from labeled cells and intracellular lactic dehydrogenase from the cells and decrease in cell viability demonstrated by the trypan blue exclusion test. The three parameters were quantitatively parallel to one another under various experimental conditions, namely different periods of irradiation and irradiation in the presence of different concentrations of melanin. The above effects were more pronounced when the irradiation was carried out in the presence of melanin from red hair than in the presence of black-hair melanin. In the absence of either melanin, the irradiation did not produce any significant effect in cell viability or cell lysis. Irradiation of the cells in the presence of red-hair melanin also decreased the transplantability of these cells. These observations clearly show that irradiation of cells in the presence of pheomelanin could produce cytotoxic effects. The present experimental design may have application in the development of in vitro models for the study of UV radiation-induced cutaneous carcinogenesis. The reactions of pheomelanin may be related to the susceptibility of "Celtic" skin to UV radiation-induced skin damage and carcinogenesis.

Animals↗

Eumelanins and pheomelanins: characterization by electron spin resonance spectroscopy.

Synthetic dopa melanin and cysteinyldopa melanin have different electron spin resonance spectra. Data are reported for mixtures of these melanins and for dopa-cysteinyldopa copolymers, which are spectroscopically similar. A simple parameterization of the spectra allows estimation of the relative amounts of (i) dopa melanin and cysteinyldopa melanin in mixtures and of (ii) dopa and cysteinyldopa incorporated into copolymers. Several natural eumelanins and pheomelanins have been characterized and shown to be copolymers.

Animals↗

Novel free radicals in synthetic and natural pheomelanins: distinction between dopa melanins and cysteinyldopa melanins by ESR spectroscopy.

Synthetic pheomelanins from enzymic oxidation of the 3,4-dihydroxyphenylalanine (dopa) derivative 5-S-cysteinyldopa have been examined by ESR spectroscopy. These alkalisoluble polymers contain a novel kind of free radical that is spectroscopically distinct from that found in eumelanins. Delocalization of the unpaired electron onto a nitrogen atom and the ability of the radical to chelate complexing metal ions strongly suggest an o-semiquinonimine structure. The synthetic pheomelanin was compared with natural red pigments extracted from human red hair and from red chicken feathers. Spectroscopically, the chicken feather pheomelanin is almost identical to synthetic cysteinyldopa pheomelanin. In contrast, the pigment from red hair has a major spectral component very similar to that found in dopa melanin, with a smaller component corresponding to that found in cysteinyldopa melanin.

Cysteinyldopa↗

Binding of protoporphyrin to melanin and oxidation-reduction properties of melanin-protoporphyrin complex.

The binding of protoporphyrin to melanin and the effect of the binding of protoporphyrin to melanin on the oxidation-reduction properties of melanin were studied. Various concentrations of protoporphyrin were incubated with melanin suspensions. The amounts of protoporphyrin remaining in the supernatant after sedimentation of the melanin were determined. The amount of bound protoporphyrin was determined by extraction with 3 M HCl. The results showed that when the initial concentration of protoporphyrin was varied, the amounts of protoporphyrin bound were in accordance with Langmuir's isotherm. From these results it was calculated that at infinite concentration of protoporphyrin 7.62 +/- 0.38 microgram protoporphyrin would be bound to 1 mg melanin. The activity to catalyze the coupled oxidation of NADH and reduction of ferricyanide was less in the case of the melanin-protoporphyrin complex than the free melanin. It is suggested that the binding of a naturally occurring photosensitizer such as protoporphyrin to melanin may have significant biological effects viz (i) photosensitivity due to protoporphyrin, (ii) the chemical reactivity of melanin in internal organs, and (iii) protective action of melanin in skin against ultraviolet radiation.

Ferricyanides↗

The effects of coal tar and ultraviolet radiation upon the incorporation of thymidine into DNA by Ehrlich ascites carcinoma cells in vitro.

The effects of coal tar with and without radiation from three types of sources upon the incorporation of thymidine into DNA by Ehrlich ascites carcinoma cells were investigated. It was found that addition of varying concentrations of coal tar inhibited the thymidine incorporation by progressively greater amounts. Irradiation by mercury vapor lamp or fluorescent tubes, both emitting predominantly UVA (320-400 nm) and visible radiations, inhibited the DNA synthesis to a small extent. However irradiation with either of these sources in the presence of tar gave a synergistic effect on the DNA synthesis. Irradiation with a predominantly UVB (260--320nm) source inhibited the DNA synthesis to a large extent. Irradiation with this source in the presence of coal tar did not give a synergistic effect but gave a summation effect. These findings have relevance in helping to choose the approporate radiation source for tar phototherapy of psoriasis. This in vitro system could also be used for other applications such as determining potencies of various tars or tar fractions.

Animals↗

Skin melanoma induced by 7,12-dimethylbenzanthracene in albino guinea pigs and its similarities to skin melanoma of humans.

A model for a metastasizing melanoma was developed, and its characteristics were established. Sixty-five albino guinea pigs were painted with 7,12-dimethylbenzanthracene in acetone. There was evidence that, after 18 months, 40% of the animals developed melanomas. Melanomas arose by a malignant transformation of junctional nevus cells and/or by transformation of amelanotic melanocytes. Metastases to the skin and internal organs were multiple and eventually fatal for the animals. Histology and electron microscopy of induced melanomas were reviewed in detail. Clinical and histological events leading to development of melanoma in albino guinea pigs were found to be similar to human melanomas in a number of aspects. Fragments of melanomas were successfully transplanted to "nude" mice and healthy albino guinea pigs. The described model could be used for study of the various cellular and tissue events which precede nevus, lentigo maligna, and melanoma formation. It could also be useful in studying carcinogenic potential, for studying development of metastases, and presumably for trials of treatment.

9,10-Dimethyl-1,2-benzanthracene↗

The effects of hyalurodinase upon tumor formation in BALB/c mice painted with 7,12-dimethylbenz-(a)anthracene.

Experiments were performed to investigate the effects of hyaluronidase on chemical carcinogenesis. Two experiments were carried out using BALB/c mice. In the first experiment the mice were divided into three groups, viz. (1) painted with 7,12-dimethylbenz(a)anthracene (DMBA), (2) injected with hyaluronidase and painted with DMBA and (3) injected with saline and painted with DMBA. In the second experiment the mice were divided into three groups: (1) painted with DMBA, (2) injected with hyaluronidase and painted with DMBA and (3) injected with heat-inactivated hyaluronidase and painted with DMBA. The tumor incidence and size of tumors were significantly lower in the group treated with hyaluronidase than in the other groups. The latent period was increased. The mitotic index of the skin adjacent to the tumors at the end of the experiment was decreased. These studies show that hyaluronidase can act as an anticarcinogenic agent.

9,10-Dimethyl-1,2-benzanthracene↗

Photolysis of mast cells in presence of protoporphyrin.

The effects of ultraviolet and visible irradiation in presence of protoporhyrin upon mast cells were investigated. Rat peritoneal mast cells were suspended in a medium containing varying concentrations of protoporphyrin and were irradiated using a mercury vapor lamp. The release of histamine is related to both the concentrations of protoporphyrin and the period of irradiation. Comparatively negligible amounts of histamine were released when the cells were irradiated in absence of protophyrin or when the cells were incubated in the dark in presence of protoporphyrin. When 51Cr-labelled cells were employed, the release of histamine was paralleled by the release of 51Cr. These results suggest that the release of histamine was due to the lysis of cells. It was found that 2-deoxyglucose, iodoacetate and carbonyl cyanide, m-chlorophenyl hydrazone at concentrations which are known to inhibit the secretory release of histamine or uncouple oxidative phosphorylation, had no effect on the photolysis of mast cells. When mast cells were irradiated in presence of protoporphyrin for 5 to 10 minutes and then kept in the dark, the release of histamine was greater than when the cells were irradiated but not subsequently kept in the dark. It is suggested that the initial site of photochemical lysis is at or near the cell surface.

Animals↗

Formation of melanin-tyrosinase complex and its possible significance as a model for control of melanin synthesis.

Previous reports have shown that the tyrosinase activities of melanosomes and soluble tyrosinase isolated from melanoma were diminished when these preparations were incubated with 3,4-dihydroxyphenylalanine (dopa). It was concluded from these results that the tyrosinase activities of these preparations decreased when melanin was synthesized in these systems. The present investigation has revealed that melanin synthesized in vitro from dopa formed a complex with purified mushroom tyrosinase. The addition of melanin diminished the tyrosinase activity of the sample. These results show that the formation of the melanin-tyrosinase complex results in a decrease in the activity of the tyrosinase solution. The tyrosinase activity of the melanin-tyrosinase complex could not be increased by certain procedures which were previously found to enhance the tyrosinase activity of isolated melanosomes.

Catechol Oxidase↗

The use of freeze-fracture and negative staining techniques to study the ultrastructure of melanosomes isolated from B16 melanoma.

Freeze-fracture negative staining methods were used to investigate the structure of melanosomes isolated from B16 melanoma. The findings demonstrated the presence of a melanosomal double-layered membrane. Negative staining procedure showed that the melanosomal membrane is sometimes ruptured, displaced or peeled off during the purification process. Fractured melanosomes showed melanin spheres with a mean diameter of 24 nm. This compares with a mean diameter of 26 nm for the melanin spheres revealed by negative staining. The granular appearance of fractured mature melanosomes is due to the fracture following a random path between melanin spheres.

Animals↗

Junctional and compound pigmented nevi induced by 9, 10-dimethyl-1,2-benzanthracene in skin of albino guinea pigs.

Seventy albino guinea pigs were used in the experiment to investigate the influence of 9,10-dimethyl-1,2-benzanthracene on amelanotic melanocytes. A field 5 sq cm was marked on the flank of each animal. Hairs from these fields were clipped twice a week and painted for 20 consecutive weeks with 0.3 ml of 1% 9,10-dimethyl-1,2-benzanthracene in acetone. During the 1-year observation period, pigmented sports appeared in 40 animals. Biopsies were taken under local anesthesia, and sections were prepared for light and electron microscopic observations. Melanin formation of unknown mechanism took place in the epidermal melanocytes and in the melanocytes from the outer root sheath. These melanocytes also formed junctional and compound nevi; serial sections revealed various stages of pigmented nevi development. Schwann cells did not participate in the formation of nevi. Evidence is presented that 9,10-dimethyl-1,2-benzanthracene can convert amelanotic melanocytes into melanin-producing cells in the albino guinea pig skin. In addition, this system produces an animal model for the development of junctional and compound nevi.

9,10-Dimethyl-1,2-benzanthracene↗

Porphyria cutanea tarda: comparison of cases precipitated by alcohol and estrogens.

A group of seven patients with porphyria cutanea tarda (PCT) precipitated by excessive alcohol consumption (A) was compared with a group of nine patients with PCT precipitated by estrogen therapy (B). Comparison was based on clinical signs, biochemical and morphologic evidence of liver disease, results of serum iron studies and response to therapy. Group A patients were men of mean age 57 years; group B patients were women of mean age 39 years who had been taking estrogen orally, either for contraception (in combination with progesterone) or as replacement therapy. Clinical signs were essentially the same in the two groups. Some patients in both groups had biochemical and morphologic evidence of liver disease. Group A patients had elevated values for serum iron and total iron-binding capacity, whereas patients in group B had normal or low values. Cessation of estrogen therapy of less than a year's duration brought about a spontaneous clinical and biochemical remission in group B patients. Otherwise, phlebotomy seemed to be the therapy of choice in both groups.

Adult↗