DNA base modifications in chromatin of human cancerous tissues

Abstract

Free rudi&induscd damegc to DNA in vivo is implicated to play II role in cwcinogcncris. Ewidcncc exists thal DNA dnmnpc by cndoynous free radiuls occurs in vivo, und thcrc is a rtcadpstatc lwcl of free radic&moditIcd hascs in ccllullrr DNA. WC hove invaligPtcd cndogcnous lcvcls of typical free rztdic&induscd DNA bits modifications in chromriz of various human cancerous tissues and their canswfrec rurrounding~issucr.Five different lypcr of sur@cally rcmovcd tirsucr were UK& nttmcly eolon, stomach. ovary, brain and lung tissues. In chromntin samples ivolatcd fram thcsc tissues. iivc pyrimidinedcrivcd and six purinc-dcrivcd modillcd DNA busts wcrc idcntincd and quantitatcd by ~schromatographyltnass spsctromctry with rslcctcd.ion monitoring, Thcsc wcrc 5.hydrox~S~mcthylhydantoin, 5.hydroxyhydantoin, 5~(hydroxymcthyl)urcil, S.hydroxycy. torinc, 5,6.dihydroxycyt6dac. 4.6~diamino.S-formnmidopyrimidinc.t.hydr.rxyudcninc, xnnthinc, I.hydronyodcninc, 2,6diaminc&hydron~5. furmnmidopyrimidinc, and 8*hydroxy8uaninc. That compounds arc known to bc formed typically by hydroxyl rsdisal attach on DNA bw. In all ems, clcvatcd umounts over control lcvcls of modifIcd DNA bares WCFC found in cancerous tirrucr. The umounta of modified beset dcpndcd nn the tiwc type, Lung tissues rcmovcd from mokcrs hlrd the highest incrcnrlr of modified bases ubovc the conrrol Icvcls, and the hifisst overall umounts, Colon cunscr tissue samples hurl the lowcrt lncrcuscs of mdiClcd bttscs over the control Icwls. The results clearly indicate hi&r rtcady&!tc lcvclr of moditlcd DNA basss in cancerous tirsucr thaw in their cunccr.frcc surrounding tirruss~ Some of thcsc l-ions arc known lo tx promutagenic. although others have not been invcrriylltcd for their mutpycnicity, Identified DNA lctions mny play B cwsativc role in atrcinoycncr!r.

Reversible zinc exchange between metallothionein and the estrogen receptor zinc finger

“…Binding of metal-depeted ER to DNA was restored physiologival relevance of "OH radical induced DNA modifiby the addition of either 700 ktM zinc acetate or 140 ktM cations is an important one since "OH radicals have been native MT. Binding increased in a dose-dependent manner reported in many cancerous human tissues [23,24]. A recent in the presence of either zinc acetate or MT.…”

Persistent oxidative stress in colorectal carcinoma patients

“…Furthermore, many observations indicate a direct correlation between 8-oxoGua formation and carcinogenesis in vivo. 6,7,10,11 We have demonstrated elevated levels of typical free radicalinduced DNA base modification, including 8-oxoGua, in human cancerous colon tissues when compared to cancer free surrounding tissues. 6,7,12 These data were confirmed by Condo et al 13 who demonstrated higher amounts of 8-oxodGuo in colorectal carcinoma cells.…”

DNA Sequence Context Effects on the Glycosylase Activity of Human 8-Oxoguanine DNA Glycosylase

“…In this regard, G to T transversions at TP53 mutational hot spots have been detected in several carcinomas (21)(22)(23). These mutations may be related to 8-oxoG, because elevated levels of 8-oxoG have been found in several carcinomas (24,25). Interestingly, formation of 8-oxoG at CpG dinucleotides in the gene promoter region inhibits the binding of methyl-CpG-binding proteins and the SP1 transcription factor (26,27).…”