Protection by methylproamine of irradiated human keratinocytes correlates with reduction of DNA damage

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.

On the symbiosis of law and truth in Christian theology: Reconciling universal and particular through the Pauline law of love

This article argues that the secular liberal and positivist foundations of the modern Western legal system render it violent. In particular, the liberal exclusion of faith and subjectivity in favour of abstract and universal reason in conjunction with its privileging of individual autonomy at the expense of the community leads to alienation of the individual from the community. Similarly, the positivist exclusion of faith and theology from law, with its enforced conformity to the posited law, also results in this violence of alienation. In response, this article proposes a new foundation for law, a natural law based in the truth of Trinitarian theology articulated by John Milbank. In the Trinity, the members exist as a perfect unity in diversity, providing a model for the reconciliation of the legal individual and community: the law of love. Through the law of love as the basic norm, individuals love their neighbours as themselves, reconciling the particular and the universal, and providing a community of peace rather than violence.