[a] GokÅeS erindere, [a] and Melike Ozder [a] 1IntroductionTe mozolomide( TMZ) is an ew class of imidazotetrazinone derivatives and an oral alkylating agent approved by the Food and Drug Administration (FDA) for the treatment of glioblastoma multiform and recurrent anaplastic astrocytoma [1].T MZ enters the cerebrospinal fluid and readily crosses the bloodÀbrain barrier so it is of special interest in central nervous systems tumors. TMZ contains three adjacent nitrogen atoms and presents unique physicochemical properties and much greater anti-cancer activity than the previously synthesized bicyclic triazenes, whichc ontaino nly two adjacent nitrogen atoms [2].TMZ is substantially stable under acid conditions. This means that it can be administeredo rallyi nc apsules.T he rate of degradation increases rapidly on passing through neutralt ob asic pH [3].U nder physiologicalc onditions, TMZ is rapidly hydrolyzed and convertedi nto activem etabolite 5-(3-methyltriazeno) imidazole-4-carboxamide (MTIC) without the need for enzymatic demethylation in the liver. TMZi sn ot active until it is converted to MTIC at physiologic pH. Thes pontaneous conversiono fT MZ to MTIC is initiated by the effecto fw ater at the highly electropositive C4 position of TMZ. This activity opens the ring,releases CO 2 and generates MTIC.MTIC is then hydrolyzed to 5-amino-imidazole-4-carboxamide (AIC) [4].A IC is additionally converted to am ethyldiazonium cation that is capable of alkylating DNAf rom the O6 and N7 positions on guanine and N3 positiono na denine.T he attack causes the transfer of am ethyl groupf rom the ion to form amethylated-DNAa dduct.Alkylation/methylationa tt he O6 position of guanine leads to mispairing with thymine,D NA double-strand breaks and cell cycle arrest and eventual apoptosis of the affected cell [3,5].T MZ showsi ts anti-cancer characteristics by methylationo fD NA.D NA methylation (addition of am ethyl groupt ot he 5 carbon of cytosine base)i sa n epigenetic alteration and ap romising biomarker for detection of variousc ancer types including breast [6],l ung [7],p rostate [8] and ovarian cancer [9].F or instance,h ypermethylation of the CpG islands (region rich in cytosine and guanineb ases)a tt he promoter region of Glutathione S-Transferase P-1 (GSTP-1) gene has been widely introduced as one of the promising biomarker of the prostate cancer due to being presenti nn early 90 %o f prostate cancer cases but not in normalp rostate tissues [10]. GSTP-1 is mainly related to eliminationo fp otentially toxic compounds in the cell. These functions of GSTP-1 help protect cells from metabolites of carcinogens and thus any alteration of this gene could result in DNAd amage.Abstract:A ne lectrochemicald rug-DNAb iosensor was developed for the detection of interaction between the anti-cancer drug, Te mozolomide (TMZ), and DNAs equences by using Differential Pulse Voltammetry at the graphite electrode surfaces.T MZ is ap ro-drug anda na lkylatinga gent thatc rosses the blood-brain barrier,s oi ti s mainly used for bra...