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Possible relationship between abnormal melanosome structure and cytotoxic phenomena in malignant melanoma
J Borovanský1, P Mirejovský, P A Riley
1Department of Biochemistry, 1st Faculty of Medicine, Charles University, Czechoslovakia.
Abstract:
Melanogenesis has been regarded as a hazard for pigment cells which are endangered by reactive quinones and semiquinones generated by this process. Normally the potentially cytotoxic species are confined to melanosomes by a limiting membrane and thus separated from the rest of the cell. Our electron microscopic investigation has demonstrated the presence of abnormal and incomplete melanosomes in human melanomas from epidermal and mucosal sites, in melanoma metastases, and in B16 mouse melanoma. We conclude that significant leakage of reactive melanin precursors including free radical species may occur from aberrant melanosomes in pigmented tumors. This would be expected to be reflected by fully extended physiological scavenging mechanisms, and by local and distant manifestations of cytotoxicity: Among these manifestations is free radical damage to the liver, detected by a thiobarbituric acid-reactive substances assay, in B16 melanoma-bearing mice. The efflux of toxic species from abnormal melanosomes may explain both the observed frequent occurrence of necrosis in melanomas and the therapeutic efficacy of tyrosinase substrates and may also be one of the factors influencing the extent of melanogenuria.
Insights
Aberrant melanosomes in melanomas may leak toxic melanin precursors, causing cell damage. This leakage could explain melanoma necrosis and treatment responses.
Area of Science:
- Cell Biology
- Oncology
- Biochemistry
Background:
- Melanogenesis produces reactive species harmful to pigment cells.
- Normally, melanosomes contain these cytotoxic species, protecting the cell.
Purpose of the Study:
- To investigate melanosome structure in melanomas.
- To explore the consequences of melanosome abnormalities in pigmented tumors.
Main Methods:
- Electron microscopy of human and mouse melanomas.
- Thiobarbituric acid-reactive substances assay for liver damage in mice.
Main Results:
- Abnormal and incomplete melanosomes were observed in various melanomas.
- Evidence of free radical damage to the liver was found in B16 melanoma-bearing mice.
Conclusions:
- Aberrant melanosomes may release toxic melanin precursors and free radicals.
- This leakage may contribute to melanoma necrosis and influence treatment outcomes.