Mo reo ver, the sedentary daily energyexpendi ture has been shownto corre la teclose lywith fatfree bodymass and BMI. Althoughnot measu red, th isef fectmayh ave been re la tedto a decreasein themetabolicrateduetothecalorierestric tion. Intwo sub jects ahigh in ta reasch Honokiol keoffruitand vegetab les ascomparedtoanisoc aloricdietwithnoneoftheseconlponentsreducedtheexcretionof th ymidineglycolsubs tantially, supposed lydi retodiffe rencesin antioxidant content. Inwomen athighriskof breast can ceralowfatd ietdec reasedoxid a ti ve D N A damagein nuclea ted periphe ralblood cells as measu redby the leve lsofoxidizedth ymine. Inaconlparisonofirra di atedmiceand humansthe re lati ve increaseinth ymidineglycolexcretion wassimilarinthetwospecies anddirectlyproportion alwiththeradi ation do se. Apro tectiveef fectofd ie ta ry antioxidants tow ardsoxidative D N A damage has been suggestedby obse rvationsintwo sub jectsbut needstobeconfirmedinla rge sca leinterventionstird ies, pre fe rablyincliding smokers.Inmamm ali ancellsasimilarenzymec omplex has beensh owntorepairby exc iss ion at adiffe rentsite, theprox im alanddis talphosphod ies terbondat the and sideof les ion, respective ly. Mo reo ver, G T transversions are among the most fre quenthot spotmutationsinthep supp ressorgeneinhumant umors. Ionizingrad iation and some cancerchemo the ra peutics thatindu ceox idati ve D IVA damage areknownto cause cancerinhi rmans. In th is con text, the effectof smokingin termsofoxid a ti ve D N A damage is equiva lenttoa rad iation doseof. M anyotherimport ant and age re la ted diseases, such as atherosc leros is, arethoughttoinvolve ROS re la ted cellul ardamagesin their pathogenes is. The pos tu la ted benefici aleffectsofantioxidantsupplementation andotherdietaryin tervention alsorep re sentilnch allengedh ypo the sestobetes ted. Carcnogenesis. . D N A damageinducedbyasbestosintl iepresenceofhyd rogen per oxide.G ann. : i I D E M I O L O G I C APPL ICAT IONS H YDRO X YD EO X YGU ANO S IN E AS A B IOMARKER ii r.. qlr I, rat renalsarcomas indu ced. . C iga rette smoking induces fo rmationof li yd roxydeoxyg tanosinc, oneof the ox idati ve D N A damages n licrman periphe ralleucocy tes. Met aboli sm. . D N A basemodification in ch romatinofhum ancance rous tissues.Ldr cet: l. Na lcire. Nephron. Ne verthe less, rtobecarcinogenicin ex imentald atareve aledt chromosomalb rea kage workersocccrpationallyinmutagenicp aramete This resea rcli has been part Address corrcsporldencelo IST, Vrale Benedetto XV, journalofToxic What generates the DNA damage signal at mammalian chromosome ends or at other doublestrand breaks is not known.Telomere dysfunction is often accompanied by disappearance of the telomeric overhang, raising the possibility that DNA degradation could generate the structure that signals.Here we address these issues by studying telomere structure after conditional deletion of mouse TRF, the protective factor at telomeres.Upon removal of TRF from TRFF p mouse embryo fibroblasts, a telomere damage response is observed at most chromosome ends.As expected, the telomeres lose the overhang and are processed by the nonhomologous endjoining pathway.Notably, the telomeres retained their overhangs, but they were recognized as sites of DNA damage, accumulating the DNA damage response factors BP and HAX, and activating the ATM kinase.Thus, activation of the ATM kinase pathway at chromosome ends does not require overhang degradation or other overt DNA processing.