Effect of Melanin on Radiation Response of CHO Cells

Hopwood, Larry E.; Swartz, Harold M.; Pajak, Stanislawa

doi:10.1080/09553008514550761

Cited by 21 publications

(15 citation statements)

References 14 publications

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“…Electron microscopy study showed that cells from dark appearing spheroids contained high concentrations of melanosomes (Szekely et al, 1985). Two studies showed that the addition of exogenous melanin in CHO cells or the variation of melanin content in B16 melanoma cells did not influence radiation sensitivity (Hopwood et al, 1985;Stephens et al, 1986). Our results on R25 confirm this finding and further indicate that melanin content over the range found in the white, brown and black spheroids also did not influence thermal sensitivity.…”

supporting

confidence: 81%

Radiation, heat and anti-melanin drug response of a transformed mouse embryo cell line with varying melanin content

Raaphorst

Azzam²

1987

Br J Cancer

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supporting

confidence: 81%

Radiation, heat and anti-melanin drug response of a transformed mouse embryo cell line with varying melanin content

Raaphorst

Azzam²

1987

Br J Cancer

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“…41 Studies on Chinese hamster-human hybrid ovary cells transfected with the tyrosinase gene demonstrated that melanin production protected against gamma radiation, 42 but in Chinese hamster ovary cells (melanin is incorporated by endocytosis) there was lack of protection against X-rays. 24 Likewise, Grossi et al 43 did not find melanin protection when studying the survival of human mammary epithelial cells incubated with melanin followed by exposure to X-rays and alpha particles. It is therefore possible that the protective activity of melanin requires selective association with melanocytes.…”

Section: Discussionmentioning

confidence: 99%

“…Melanotic and amelanotic melanomas differ in their sensitivity to ionizing and UVR, [22][23][24][25] suggesting that inhibition of melanogenesis could play a role in melanoma therapy. 19 Experimentally, the significance of melanin presence for radioresistance of melanoma was described in Bomirski melanomas transplanted in hamsters, e.g., pigmented melanomas exhibited higher resistance to ionizing radiation compared to nonpigmented tumors.…”

mentioning

confidence: 99%

“…11,12,14,16 Nevertheless, the same positive capacity of melanin to scavenge free radical and ROS becomes undesirable in the response of melanoma to radio-, photo-or chemotherapy 11,16,[18][19][20] ; furthermore, the pro-oxidant properties of melanin can, in certain conditions, stimulate melanoma progression. 21 Melanotic and amelanotic melanomas differ in their sensitivity to ionizing and UVR, [22][23][24][25] suggesting that inhibition of melanogenesis could play a role in melanoma therapy. 19 Experimentally, the significance of melanin presence for radioresistance of melanoma was described in Bomirski melanomas transplanted in hamsters, e.g., pigmented melanomas exhibited higher resistance to ionizing radiation compared to nonpigmented tumors.…”

mentioning

confidence: 99%

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Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy

Brożyna¹,

VanMiddlesworth²,

Slominski³

2008

Intl Journal of Cancer

124

113

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Melanin pigment displays strong photo-and radioprotective properties, suggesting that inhibition melanogenesis could increase sensitivity of melanoma to ionizing radiation. We tested this concept in human melanoma cells cultured in either Ham's F10 medium to maintain amelanotic phenotype or DMEM to induce/stimulate melanin production, respectively; N-phenylthiourea (PTU) and Dpenicillamine were used as an inhibitor of melanogenesis. Melanogenic activity was evaluated by visual inspection (color of cell pellets) or by measurement of tyrosinase (dopa oxidase) activity assay. Amelanotic cells or cells with various melanin content were exposed to gamma radiation and tested for viability and colony forming capability. Gamma radiation at doses of 2-15 Gy inhibited cell viability and colony forming efficiency in dose-and timedependent manner, but pigmented melanoma cells were significantly more resistant to gamma radiation than nonpigmented cells (p < 0.05-0.001). Both PTU and D-penicillamine inhibited strongly tyrosinase activity and melanin production in melanoma cells (p < 0.05-0.001). Furthermore, inhibition of melanogenesis by PTU or D-penicillamine resulted in enhancement of melanoma cells sensitivity to killing by gamma rays. In conclusion, the results of these cell culture experiments give support to a clinical trial of pharmacologically induced decrease in melanin synthesis to enhance the efficacy of radiotherapy in advanced melanomas. ' 2008 Wiley-Liss, Inc.Key words: melanogenesis; melanin; melanoma; tyrosinase; gamma radiation Melanoma is the tumor with the most rapidly increasing incidences worldwide and it is predicted that by 2010, 1 person out of 50 white persons will be affected by this disease.1 Surgical excision is an effective treatment for early-stage melanomas (localized to the skin), and it is widely accepted that melanoma is resistant to all therapeutic modalities once the metastatic process started. 1-4The use of radiotherapy for advanced melanoma is controversial, and it serves mainly as palliative treatment. [5][6][7][8][9] Most likely the radioresistance of melanoma is due to the presence of melanin pigment, which acts as endogenous radioprotector. 10,11The major role of cutaneous melanin is protection against the harmful actions of solar radiation, by acting as a filter against ultraviolet radiation (UVR), preventing its penetration and genotoxicity (formation of UV-induced DNA dimmers).11-16 Melanin also neutralizes reactive oxygen species (ROS) generated mostly by UVA, through its antioxidative and free-radical scavenging actions. 13,16,17 Overall, melanin protects against epidermal carcinogenesis or melanomagenesis. 11,12,14,16 Nevertheless, the same positive capacity of melanin to scavenge free radical and ROS becomes undesirable in the response of melanoma to radio-, photo-or chemotherapy 11,16,[18][19][20] ; furthermore, the pro-oxidant properties of melanin can, in certain conditions, stimulate melanoma progression. 21Melanotic and amelanotic melanomas differ in their sensitivity to...

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“…However, in other investigations, melanin was shown to be ineffective at protecting against radiation damage. The effect of melanin on the response of mammalian cells to gamma-radiation was investigated in Chinese hamster ovary cells [15] and in mouse melanoma cells [16,17]. In these experiments, the variation of melanin content inside the irradiated cells did not influence their radiation sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Melanin decreases clastogenic effects of ionizing radiation in human and mouse somatic cells and modifies the radioadaptive response

Mosse¹,

Kostrova²,

Subbot³

et al. 2000

Radiat Environ Biophys

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Melanin's influence on the chromosome aberration frequency induced by radiation in human lymphocytes and mouse bone marrow cells has been studied. We revealed earlier that melanin significantly decreases the frequencies of different radiation-induced mutations in animal germ cells. Melanin protection in somatic cells has been found to be less effective. The melanin effect in somatic cells depends on radiation dose: the lower the damage level, the better the melanin protection. In order to determine the influence of melanin at low radiation doses, the adaptive response was investigated in mouse bone marrow cells in vivo. The level of chromosome aberrations in these cells after fractionated irradiation of 0.2 Gy+1.5 Gy with a 4-h interval was about half that after a single dose of 1.7 Gy. If melanin was injected prior to irradiation, the aberration level decreased by a factor of about two in both cases. This observed result may be due to the potential radioprotective effect of melanin and to the absence of any adaptive response, whereas in the case of melanin application between the priming and challenge doses, the combined effect of the adaptive response as well as melanin protection resulted in a 4-fold decrease of chromosome aberrations. These results allow us to draw the following conclusions: adaptive response can be prevented by a radioprotector such as melanin, and melanin is capable of completely removing low-dose radiation effects.

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Effect of Melanin on Radiation Response of CHO Cells

Cited by 21 publications

References 14 publications

Radiation, heat and anti-melanin drug response of a transformed mouse embryo cell line with varying melanin content

Radiation, heat and anti-melanin drug response of a transformed mouse embryo cell line with varying melanin content

Inhibition of melanogenesis as a radiation sensitizer for melanoma therapy

Melanin decreases clastogenic effects of ionizing radiation in human and mouse somatic cells and modifies the radioadaptive response

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