False precursors of melanin as selective melanoma seekers

Dencker, Lennart; Larsson, Bengt; Olander, Karin; Ullberg, Sven; Yokota, Mako

doi:10.1038/bjc.1979.80

Cited by 46 publications

(25 citation statements)

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“…In the present study we have expanded the results from a previous investigation (Dencker et at., 1979). The following experiments have been performed:…”

mentioning

confidence: 56%

“…In a preliminary report, we earlier showed that thiouracil strongly accumulates in growing melanin, for example in the eyes of young animals and in melanotic melanomas. Thiouracil is apparently used as a false precursor in the synthesis of melanin (Dencker et al, 1979;1981). The mechanism for this uptake is thus different from that of many polycyclic amines (e.g.…”

mentioning

confidence: 99%

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A new melanoma seeker for possible clinical use: Selective accumulation of radiolabelled thiouracil

Dencker¹,

Larsson²,

Olander³

et al. 1982

Br J Cancer

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Summary.-In a previous report we have shown that a few substances, especially thiouracil, are incorporated as false precursors into melanin during its synthesis.In the present investigation, we have intensified our studies on the incoporation of thiouracil into melanotic melanomas. Firstly, the distribution and retention of both 14C-and 35S -labelled thiouracil in mice with transplanted melanomas were studied.

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“…In the present study we have expanded the results from a previous investigation (Dencker et at., 1979). The following experiments have been performed:…”

mentioning

confidence: 56%

mentioning

confidence: 99%

A new melanoma seeker for possible clinical use: Selective accumulation of radiolabelled thiouracil

Dencker¹,

Larsson²,

Olander³

et al. 1982

Br J Cancer

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“…2-Thiouracil, which is the most studied substancc in this rcgard, strongly nccumulates in the pigmented tissues of fetal eyes, where the rate of melanin synthesis is high, but in the adult eye, where the melanin synthesis is low, only minute amounts of thiouracil are accumulated (Dencker et al, 1979). The uptake in melanin is thus related to the melanin synthesis rather than to the occurrence of preformed melanin-thiouracil is lacking affinity to the preformed melanin (Dencker et al, 1981).…”

Section: Modiolus Brainmentioning

confidence: 94%

Interaction Between Chemicals and Melanin

Larsson

1993

Pigment Cell Research

261

182

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Various drugs and other chemicals, such as organic amines, metals, polycyclic aromatic hydrocarbons, etc., are bound to melanin and retained in pigmented tissues for long periods. The physiological significance of the binding is not evident, but it has been suggested that the melanin protects the pigmented cells and adjacent tissues by adsorbing potentially harmful substances, which then are slowly released in nontoxic concentrations. Long-term exposure, on the other hand, may build up high levels of noxious chemicals, stored on the melanin, which ultimately may cause degeneration in the melanin-containing cells, and secondary lesions in surrounding tissues. In the eye, e.g., and in the inner ear, the pigmented cells are located close to the receptor cells, and melanin binding may be an important factor in the development of some ocular and inner ear lesions. In the brain, neuromelanin is present in nerve cells in the extrapyramidal system, and the melanin affinity of certain neurotoxic agents may be involved in the development of parkinsonism, and possibly tardive dyskinesia. In recent years, various carcinogenic compounds have been found to accumulate selectively in the pigment cells of experimental animals, and there are many indications of a connection between the melanin affinity of these agents and the induction of malignant melanoma.

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“…Numerous studies in rodents have documented the selective uptake of CPZ and related compounds by cells containing melanin (Blois, 1965;Fairchild et al, 1982a;Nakanishi, Ichihashi and Mishima, 1981;Nakanishi etal, 1980;Potts, 1964) and of TU by cells actively synthesizing melanin (Broxterman et al, 1983;Dencker et al, 1979;Dencker et al, 1982;Fairchild et al, 1982b;. Encouraging results have been obtained supporting a possible diagnostic and/or therapeutic role of radiopharmaceutical analogues for malignant melanoma.…”

Section: Introductionmentioning

confidence: 99%

Accumulation of Chlorpromazine and Thiouracil by Human Melanoma Cells in Culture

Parsons

Allen

1986

Aust J Exp Biol Med

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Summary.The uptake (total radioactivity in intact cells) and incorporation (radioactivity bound to acid-precipitable material) of '^C-chlorpromazine (CPZ) and '•'C-thiouracil (TU) were studied using a library of 3 human fibroblast strains and 13 tumour cell lines. In contrast to previous studies using rodent melanomas in vivo, the melanoma lines, including lines with high tyrosinase and melanin contents, did not take up more CPZ and TU than non-melanoma cells (fibroblasts, HeLa cells). Incorporation of CPZ was also broadly similar in all cell types studied. TU was selectively incorporated into the melanoma line having a high tyrosinase and melanin content but not into lines with high tyrosinase activity and low melanin content. While supporting the possibility of selective therapy for heavily-pigmented melanomas using labelled TU derivatives, these results suggest that the action of potentially melanoma-affined compounds should be further evaluated in human cells. Unlabelled CPZ or TU was not selectively toxic to melanoma cells. Unexpectedly, methylation-sensitive tumour cells (Mer" phenotype) were highly resistant to TU, thus providing a new experimental tool for understanding the genesis of this phenotype in vivo.

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False precursors of melanin as selective melanoma seekers

Abstract: Images Fig. 1 Fig. 2

Cited by 46 publications

References 1 publication

A new melanoma seeker for possible clinical use: Selective accumulation of radiolabelled thiouracil

A new melanoma seeker for possible clinical use: Selective accumulation of radiolabelled thiouracil

Interaction Between Chemicals and Melanin

Accumulation of Chlorpromazine and Thiouracil by Human Melanoma Cells in Culture

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