Protection by methylproamine of irradiated human keratinocytes correlates with reduction of DNA damage
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01/03/2011
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Resumo |
Purpose: The therapeutic ratio for ionising radiation treatment of tumour is a trade-off between normal tissue side-effects and tumour control. Application of a radioprotector to normal tissue can reduce side-effects. Here we study the effects of a new radioprotector on the cellular response to radiation. Methylproamine is a DNA-binding radioprotector which, on the basis of published pulse radiolysis studies, acts by repair of transient radiation-induced oxidative species on DNA. To substantiate this hypothesis, we studied protection by methylproamine at both clonogenic survival and radiation-induced DNA damage, assessed by γH2AX (histone 2AX phosphorylation at serine 139) focus formation endpoints. Materials and methods: The human keratinocyte cell line FEP1811 was used to study clonogenic survival and yield of γH2AX foci following irradiation (137Cs γ-rays) of cells exposed to various concentrations of methylproamine. Uptake of methylproamine into cell nuclei was measured in parallel. Results: The extent of radioprotection at the clonogenic survival endpoint increased with methylproamine concentration up to a maximum dose modification factor (DMF) of 2.0 at 10 μM. At least 0.1 fmole/nucleus of methylproamine is required to achieve a substantial level of radioprotection (DMF of 1.3) with maximum protection (DMF of 2.0) achieved at 0.23 fmole/nucleus. The γH2AX focus yield per cell nucleus 45 min after irradiation decreased with drug concentration with a DMF of 2.5 at 10 μM. Conclusions: These results are consistent with the hypothesis that radioprotection by methylproamine is mediated by attenuation of the extent of initial DNA damage. |
Identificador | |
Publicador |
Informa Healthcare |
Relação |
DOI:10.3109/09553002.2011.530333 Lobachevsky, Pavel N., Vasireddy, Raja S., Broadhurst, Sam, Sprung, Carl N., Karagiannis, Tom C., Smith, Andrea J., Radford, Ian R., McKay, Michael J., & Martin, Roger F. (2011) Protection by methylproamine of irradiated human keratinocytes correlates with reduction of DNA damage. International Journal of Radiation Biology, 87(3), pp. 274-283. |
Direitos |
Copyright 2011 Informa UK, Ltd. |
Fonte |
Faculty of Health |
Palavras-Chave | #111200 ONCOLOGY AND CARCINOGENESIS #human keratinocytes, ionising radiation, DNA breaks, radioprotection, DNA ligands |
Tipo |
Journal Article |