Uphononongo lwezilwanyana luchaza indima yeprotheyini ye-URI ekuvuseleleni izicubu emva kokuvezwa kwidosi ephezulu yemitha yonyango.
Unyango lweMisebe okanye iRadiotherapy yindlela esebenzayo yokubulala umhlaza emzimbeni kwaye inoxanduva olukhulu lokunyusa amazinga okusinda komhlaza kwiminyaka emininzi edlulileyo. Nangona kunjalo, enye yezona zinto zingalunganga zonyango olunamandla kukuba luyonakalisa ngaxeshanye iiseli ezisempilweni emzimbeni - ngakumbi iiseli zamathumbu ezisempilweni ezisengozini - kwizigulana ezifumana unyango lomhlaza wesibindi, ipancreas, i-prostrate okanye i-colon. Olu tyhefu kunye nomonakalo wezicubu obangelwa yimitha ye-ionizing ephezulu ludla ngokuguqulwa emva kokuba unyango lwe-radiotherapy lugqityiwe, nangona kunjalo, kwizigulana ezininzi lukhokelela kwiingxaki ezifana nesifo esibulalayo esibizwa ngokuba yi-gastrointestinal syndrome (GIS). Esi sifo sinokubulala iiseli zamathumbu, ngaloo ndlela sitshabalalise amathumbu kwaye sikhokelela ekufeni kwesigulana. Akukho nyango lufumanekayo lwe-GIS ngaphandle kokunciphisa iimpawu zayo ezifana nokucaphuka, urhudo, ukopha, ukuhlanza njl.
Kwisifundo esitsha esapapashwa ngoMeyi 31 kwiSayensi, abaphandi babejonge ukuqonda iziganeko kunye neendlela ze-GIS emva kokuvezwa yimitha kwimodeli yesilwanyana (apha, impuku) ukuze kuchongwe ii-biomarkers ezinokuqikelela amanqanaba obuthi bamathumbu emva kokuba isilwanyana sichatshazelwe yimitha enzima. Bagxile kwindima yeprotheyini ye-chaperone yemolekyuli ebizwa ngokuba yi-URI (unconventional prefoldin RPB5 interactor), enomsebenzi wayo ochanekileyo awukaqondwa ngokupheleleyo. Kwisifundo sangaphambili se-in vitro seqela elifanayo, amanqanaba aphezulu e-URI abonwa ekhusela iiseli zamathumbu kumonakalo we-DNA obangelwa kukuvezwa yimitha. Kwisifundo sangoku esenziwe kwi-vivo , kwaveliswa iimodeli ezintathu zegundane ze-GIS genetic. Imodeli yokuqala yayinamanqanaba aphezulu e-URI abonakaliswa emathunjini. Kwimodeli yesibini i-URI gene kwi-intestinal epithelium yasuswa kwaye imodeli yesithathu yamiselwa njengolawulo. Onke amaqela amathathu eempuku achaphazeleka kwiidosi eziphezulu zemitha ezingaphezu kwe-10 Gy. Uhlalutyo lubonise ukuba ukuya kuthi ga kwi-70 ekhulwini yeempuku kwiqela lolawulo zafa ngenxa ye-GIS kwaye zonke iimpuku ezazicinywe yi-URI protein gene nazo zafa. Kodwa zonke iimpuku ezazikwiqela ezazinamanqanaba aphezulu e-URI zasinda ekuchatshazelweni yimitha ephezulu.
Xa iprotheyini ye-URI isetyenziswa kakhulu, ithintela ngokukodwa i-β-catenin ebalulekileyo ekuvuseleleni izicubu /amalungu emva kokukhanyiselwa kwaye ngaloo ndlela iiseli azikhuli. Ekubeni umonakalo wemitha unokwenziwa kuphela kwiiseli ezikhula ngokukhawuleza, akukho mpembelelo ibonwayo kwiiseli. Kwelinye icala, xa iprotheyini ye-URI ingabonakaliswa, ukuncipha kwe-URI kuvula i-β-catenin–induced c-MYC expression (oncogene) ebangela ukwanda kweeseli kwaye inyuse ukuthambekela kwazo kumonakalo wemitha. Ke ngoko, i-URI idlala indima ebalulekileyo ekukhuthazeni ukuvuselelwa kwezicubu ekuphenduleni ukukhanyiselwa kwemitha ephezulu.
Olu lwazi lutsha lweendlela ezibandakanyekayo kuhlaziyo lwethishu emva kokulunywa kwemitha lunokunceda ekuphuhliseni iindlela ezintsha zokufumana ukhuseleko kwidosi ephezulu yokusasazeka ngemitha emva konyango ngeradio. Uphononongo lunefuthe kwizigulane ezinomhlaza, amaxhoba eengozi ezibandakanya izityalo zenyukliya kunye nosomajukujuku.
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{Unokufunda iphepha lokuqala lophando ngokunqakraza ikhonkco le-DOI elinikwe ngezantsi kuluhlu lwemithombo ecatshulweyo (s)}
Umthombo (s)
UChaves-Pérez A. et al. 2019. I-URI iyadingeka ukugcina uyilo lwamathumbu ngexesha lemitha ye-ionizing. Science. 364 (6443). https://doi.org/10.1126/science.aaq1165
Amagqabantshintshi zivaliwe.