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Titolo:
Levels of N7-(2-hydroxyethyl)guanine as a molecular dosimeter of drug delivery to human brain tumors
Autore:
Bodell, WJ; Giannini, DD; Hassenbusch, S; Levin, VA;
Indirizzi:
Univ Calif San Francisco, Dept Neurol Surg, Brain Tumor Res Ctr, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 r, Dept Neurooncol, Houston, TX 77030 USA Univ Texas, MD Anderson Canc Ctr, Dept Neurosurg, Houston, TX 77030 USA Univ Texas Houston TX USA 77030 tr, Dept Neurosurg, Houston, TX 77030 USA
Titolo Testata:
NEURO-ONCOLOGY
fascicolo: 4, volume: 3, anno: 2001,
pagine: 241 - 245
SICI:
1522-8517(200110)3:4<241:LONAAM>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
DNA ALKYLATION PRODUCTS; PHASE-I TRIAL; MALIGNANT GLIOMA; SURVIVAL; CELLS; 1-(2-CHLOROETHYL)-1-NITROSOUREA; O-6-BENZYLGUANINE; CHEMOTHERAPY; REPAIR; INDEX;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Bodell, WJ Univ Calif San Francisco, Dept Neurol Surg, Brain Tumor Res Ctr, Box 0555,San Francisco, CA 94143 USA Univ Calif San Francisco Box 0555 San Francisco CA USA 94143 SA
Citazione:
W.J. Bodell et al., "Levels of N7-(2-hydroxyethyl)guanine as a molecular dosimeter of drug delivery to human brain tumors", NEURO-ONCOL, 3(4), 2001, pp. 241-245

Abstract

The level of N7-(2-hydroxyethyl)guanine (N7-HOEtG), one of the DNA alkylation products formed by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment, was measured in human brain tumor samples by high performance liquid chromatography with electrochemical detection. The tumors from 6 recurrent chemotherapy-naive patients with recurrent glioblastoma multiforme were analyzed as controls. The mean level of N7-HOEtG in DNA of these specimens was 0.42 pmol/mg DNA. Samples were also obtained from a patient with a recurrent glioblastoma multiforme after direct intratumoral therapy with BCNU in ethanol (DTI-015). The levels of N7-HOEtG in the samples distal, medial, and adjacent to the site of injection were 0.8, 2.6, and 369.5 pmol/mg DNA, respectively. Comparison of the level of N7-HOEtG detected in the distal. sampleafter injection with BCNU in ethanol,with the mean level of the untreated samples indicated that it was not sufficiently different to be ruled out asa chance occurrence. Comparison of the levels of N7-HOEtG in the medial and adjacent brain tumor samples with the mean level of the control samples showed values that were approximately 6- and 879-fold higher. These results demonstrate that intratumoral administration of BCNU in ethanol produces significant levels of DNA alkylation and suggest that DNA adduct measurementsprovide a unique molecular dosimeter to evaluate delivery of alkylating agents to brain tumors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/02/20 alle ore 20:39:59