[en] The DNA contained in the nucleus of each of our cells daily suffers of thousand damages caused by solar ultraviolet radiations or ionizing radiations, with a natural or not origin, agents able to modify the genetic information. This information stays stable. True caretakers of the genome repair the DNA, provided that the cell is not over-taken by the level of the attack. Alterations of the repair mechanism are at the origin of extremely severe syndromes. The failure of one of these caretakers of the genome, the O.G.G.1 gene, seems implicated in the cancer development. It can be a lead to discover a predisposition to radioinduced or caused by other toxic agents cancers. (N.C.)

[en] 8-oxo-guanine (8-oxoG) is a common and mutagenic form of oxidized guanine in DNA. This modified base is eliminated mainly through the base excision repair pathway. In human cells its repair is initiated by hOGG1, an 8-oxoG specific DNA glycosylase, capable of excising the lesion. To analyze the consequences of cellular oxidative stresses on the human OGG1 protein activity and localisation, we investigated the effects of an acute cadmium exposure of human lymphoblastoid cells on the activity of hOGG1. We show that coinciding with the alteration of the redox cellular status, the 8-oxoG DNA glycosylase activity of hOGG1 was nearly completely inhibited. However, the OGG1 activity returned to normal levels once the redox cellular status was normalized. In vitro, the activity of purified hOGG1 was found to be inactivated by cadmium and could not be reversed by EDTA. In cells, however, the reversible inactivation of OGG1 activity by cadmium was strictly associated with reversible oxidation of the protein. Moreover, the 8-oxoG DNA glycosylase activity of purified OGG1 and that from crude extracts can be modulated by cysteine modifying agents. Oxidation of OGG1 by the thiol oxidant diamide led to inhibition of the activity and a protein migration pattern similar to that seen in cadmium-treated cells. These results suggest that cadmium inhibits OGG1 activity mainly by indirect and reversible oxidation of critical cysteine residues and that excretion of the metal from the cells leads to normalization of the redox cell status and restoration of an active OGG1. The results presented here unveil a novel redox-dependent mechanism for the regulation of OGG1 activity. The effects of other cellular oxidative stresses on hOGG1 was also explored. In particular, confocal microscopy studies show the re-localisation of the protein to an insoluble nuclear fraction. (author)

[en] A graphical method is described that allows the determination of specific radioactivities of radioactively labelled hormones. This method combines the self-displacement technique, plotting bound/free ratios versus mass of unlabelled hormone or total radioactivity of labelled preparation added to the receptor preparation, and the maximal binding capacity of the labelled hormone. The procedure presented provides a more realistic specific radioactivity for use in all binding experiments. Application of the method is demonstrated for ¹²⁵I-labelled ovine prolactin, and data are presented for ¹²⁵I-labelled human choriogonadotropin and [³H]testosterone. (author)