{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T21:13:01Z","timestamp":1791148381086,"version":"4.1.0"},"reference-count":46,"publisher":"MathDoc\/Centre Mersenne","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>De nos jours, la canc\u00e9rogen\u00e8se appara\u00eet comme un processus beaucoup plus complexe que ce que l'on croyait voici une d\u00e9cennie. L'\u00e9tude du g\u00e9nome des cellules tumorales humaines a r\u00e9v\u00e9l\u00e9 un nombre de modifications g\u00e9n\u00e9tiques et \u00e9pig\u00e9n\u00e9tiques beaucoup plus grand que celui auquel on s'attendait. De plus, le d\u00e9lai qui s'\u00e9coule entre le premier \u00e9v\u00e9nement initiateur (quand sa survenue est connue avec pr\u00e9cision) et l'\u00e9mergence clinique d'un cancer peut \u00eatre tr\u00e8s long, jusqu'\u00e0 60 ans. Ce long d\u00e9lai montre que les facteurs de risque durant la petite enfance et l'enfance m\u00e9ritent une analyse critique. Les donn\u00e9es \u00e9pid\u00e9miologiques amplifient le r\u00f4le de la promotion. Par exemple, l'alcool et l'amiante ne sont pas mutag\u00e8nes, mais provoquent irritation et prolif\u00e9ration cellulaire. M\u00eame dans le cas du tabac, le r\u00f4le de la promotion appara\u00eet comme plus important que celui des mutations. Dans la canc\u00e9rogen\u00e8se humaine, les mutations initiales n'apparaissent pas comme une \u00e9tape limitante ou cruciale.<\/jats:p>\n                  <jats:p>\n                    Au total, l'\u00e9tude biologique de la canc\u00e9rogen\u00e8se a montr\u00e9 que la cellule initiatrice n'est pas affect\u00e9e passivement par l'accumulation de l\u00e9sion par les agents canc\u00e9rog\u00e8nes physiques ou chimiques. Elle r\u00e9agit par le biais d'au moins trois m\u00e9canismes : (a) en combattant contre les esp\u00e8ces actives de l'oxyg\u00e8ne (ROS) g\u00e9n\u00e9r\u00e9es par un stress oxydatif, tel que les UV ou les radiations ionisantes, (b) en \u00e9liminant les cellules l\u00e9s\u00e9es (ayant mut\u00e9 ou instables), \u00e0 travers deux voies \u2013 (\n                    <jats:italic>i<\/jats:italic>\n                    ) l'apoptose, qui peut \u00eatre initi\u00e9e par des doses aussi faibles que quelques millisieverts, \u00e9liminant ainsi les cellules comportant des g\u00e9nomes qui ont \u00e9t\u00e9 endommag\u00e9s ou mal r\u00e9par\u00e9s, (\n                    <jats:italic>ii<\/jats:italic>\n                    ) la mort de cellules durant la mitose quand les l\u00e9sions n'ont pas \u00e9t\u00e9 r\u00e9par\u00e9es \u2013, (c) en stimulant ou en activant les syst\u00e8mes de r\u00e9paration de l'ADN. De plus, les syst\u00e8mes de communication intercellulaire informent une cellule des dommages subis par ses voisines. Un syst\u00e8me d'induction intercellulaire de l'apoptose existe et des cellules non transform\u00e9es peuvent trier s\u00e9lectivement les cellules transform\u00e9es.\n                  <\/jats:p>\n                  <jats:p>L'analyse transcriptionnelle moderne des g\u00e8nes cellulaires faisant appel \u00e0 la technologie de puces \u00e0 ADN r\u00e9v\u00e8le que de nombreux g\u00e8nes sont activ\u00e9s par des doses d'agents canc\u00e9rog\u00e8nes beaucoup plus faibles que celles pour lesquelles la mutagen\u00e8se est observ\u00e9e. Ces m\u00e9thodes ont \u00e9t\u00e9 la source d'un progr\u00e8s consid\u00e9rable. Autrefois on pensait que la canc\u00e9rogen\u00e8se \u00e9tait initi\u00e9e par des l\u00e9sions du g\u00e9nome affectant par hasard quelques cibles sp\u00e9cifiques (proto-oncog\u00e8nes, g\u00e8nes suppresseurs, etc.). Ce mod\u00e8le relativement simple a \u00e9t\u00e9 remplac\u00e9 par un autre, plus complexe, dans lequel la relation entre les cellules initi\u00e9es et leur microenvironnement joue un r\u00f4le essentiel.<\/jats:p>\n                  <jats:p>Ainsi, le processus canc\u00e9rog\u00e8ne est contrebalanc\u00e9 par des m\u00e9canismes de d\u00e9fense efficace dans la cellule, les tissus et l'organisme. En ce qui concerne le tissu, les m\u00e9canismes qui gouvernent l'embryogen\u00e8se et r\u00e9gissent la r\u00e9paration des tissus apr\u00e8s une agression apparaissent comme jouant aussi un r\u00f4le important dans le contr\u00f4le de la prolif\u00e9ration cellulaire. Ceci est particuli\u00e8rement le cas quand une cellule transform\u00e9e est environn\u00e9e de cellules normales, qui apparaissent comme \u00e9tant capables d'inhiber sa prolif\u00e9ration. La d\u00e9sorganisation tissulaire par inflammation ou la mort d'une large proportion de cellules facilite souvent l'\u00e9chappement de cellules initi\u00e9es et l'\u00e9mergence d'un clone de cellules pr\u00e9-n\u00e9oplastiques ou n\u00e9oplastiques. L'efficacit\u00e9 de l'immunosurveillance est aussi d\u00e9montr\u00e9e par le large accroissement de l'incidence de plusieurs types de cancers parmi les personnes immunod\u00e9prim\u00e9es.<\/jats:p>","DOI":"10.1016\/j.crvi.2007.03.003","type":"journal-article","created":{"date-parts":[[2007,4,17]],"date-time":"2007-04-17T07:17:27Z","timestamp":1176794247000},"page":"114-125","source":"Crossref","is-referenced-by-count":10,"title":["G\u00e9n\u00e9ralit\u00e9s sur la canc\u00e9rogen\u00e8se\u2606\u2606Ce texte est tr\u00e8s largement inspir\u00e9 par l'appendice sur la canc\u00e9rogen\u00e8se r\u00e9dig\u00e9 par R. Monier et moi-m\u00eame pour le rapport sur les causes du cancer en France. L'auteur remercie beaucoup R. Monier pour les nombreuses et fructueuses discussions qu'il a eues avec lui."],"prefix":"10.5802","volume":"331","author":[{"given":"Maurice","family":"Tubiana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3842","published-online":{"date-parts":[[2007,4,16]]},"reference":[{"key":"key2025102316302277888_1","first-page":"89","article-title":"Damage pattern as a function of radiation quality and other factors","volume":"322","author":"Burkart, W.","year":"1999","unstructured":"[1] Burkart, W. et al. Damage pattern as a function of radiation quality and other factors, C. R. Acad. Sci. Paris, Ser. III, Volume 322 (1999), pp. 89-101","journal-title":"C. R. Acad. Sci. Paris, Ser. 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