La prévention du cancer et la relation dose–effet : l’effet cancérogène des rayonnements ionisants ☆

摘要: Cancer prevention has to be based on robust biological and epidemiological data, therefore its reappraisal becomes mandatory in view of recent progress the understanding carcinogenesis. The first phase carcinogenic process, that initiation, is generally associated with mutation; however role extrinsic mutagens less critical than was thought two decades ago. During intracellular oxygen metabolism, reactive species (ROS) are made which potent mutagens. Defense mechanisms against these intrinsic include scavenger enzymatic systems destroy them (catalase, superoxide dismutase). When radiation dose low, DNA repair very effective as well elimination cells unrepaired or misrepaired DNA. Therefore a small increase number ROS, such caused by most probably no significant effect risk damage. These conclusions consistent concept practical threshold. second phase, promotion, appears key one. promotion initiated must acquire new properties (immortalization, release angiogenic factors, resistance hypoxia, etc.) order become precancerous. This evolution due accumulation genome 6 10 alteration defects. In clone cells, occurrence one cell mutation an epigenetic event gives birth subclone. There Darwinian type competition between subclones those more rapid growth because dominant (the acceleration rate can shorter cycles alleviation proliferation exerted neighboring microenvironment). genomic events provoke appearance growing rapidly having greater autonomy. process slow specific genetic favour this seldom occur. Promoting factors agents either perturb intercellular signalling stimulate (e.g. hormones) mortality: mechanical chemical irritation alcohol, bacteria, viruses) thereby inducing compensatory proliferation. Thus, gradually precancerous able divide ends when subclone acquired capacity autonomous third progression during proliferate regularly without any stimulation. lesions polyps) acquires invading surrounding tissue metastasize. whole slow, extending over several decades, mutations occur probability same lineage small. It accelerated intense stimulation instability. Ionizing radiations act firstly mutagen, high they also kill proportion homeostatic mechanism induce clonal amplification. been claimed even smallest cancer. LNT model it not scientific evidence. fuelled fear had detrimental consequences. Conversely efficacy defense radiocarcinogenesis, particularly disorganized, explain lack contamination doses radium thorium observed dial painters patients injected thorotrast. study cancers treated radiotherapy could provide important information should actively pursued aims: reduce incidence cancers; better understand radiocarcinogenesis relation effect.