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Titolo:
Circadian variation in O-6-alkylguanine-DNA alkyltransferase activity in circulating blood mononuclear cells of healthy human subjects
Autore:
Marchenay, C; Cellarier, E; Levi, F; Rolhion, C; Kwiatkowski, F; Claustrat, B; Madelmont, JC; Chollet, P;
Indirizzi:
INSERM, U484, Clermont Ferrand, France INSERM Clermont Ferrand FranceINSERM, U484, Clermont Ferrand, France Ctr Jean Perrin, Clermont Ferrand, France Ctr Jean Perrin Clermont Ferrand France errin, Clermont Ferrand, France Hop Paul Brousse, Lab Rythmes Biol & Chronotherapeut, Villejuif, France Hop Paul Brousse Villejuif France & Chronotherapeut, Villejuif, France Hop Neurocardiol, Serv Radiopharm & Radioanal, Lyon, France Hop Neurocardiol Lyon France Serv Radiopharm & Radioanal, Lyon, France
Titolo Testata:
INTERNATIONAL JOURNAL OF CANCER
fascicolo: 1, volume: 91, anno: 2001,
pagine: 60 - 66
SICI:
0020-7136(20010101)91:1<60:CVIOAA>2.0.ZU;2-8
Fonte:
ISI
Lingua:
ENG
Soggetto:
O-6-METHYLGUANINE-DNA METHYLTRANSFERASE ACTIVITY; METASTATIC COLORECTAL-CANCER; O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; BUTHIONINE SULFOXIMINE; ALKYLATING-AGENTS; FOLINIC ACID; DNA; REPAIR; OXALIPLATIN; RHYTHMS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
56
Recensione:
Indirizzi per estratti:
Indirizzo: Marchenay, C Bur Rech Clin, 58 Rue Montalembert,BP 392, F-63011 Clermont Ferrand 1, France Bur Rech Clin 58 Rue Montalembert,BP 392 Clermont FerrandFrance 1
Citazione:
C. Marchenay et al., "Circadian variation in O-6-alkylguanine-DNA alkyltransferase activity in circulating blood mononuclear cells of healthy human subjects", INT J CANC, 91(1), 2001, pp. 60-66

Abstract

Cytotoxic agents such as chloroethylnitrosoureas (CENUs) mostly alkylate DNA on the O-6-guanine position. This highly mutagenic lesion can be repaired by O-6-alkylguanine-DNA alkyltransferase (ACT), which removes the alkyl group by accepting it to the cysteine residue of its active site. ACT activity displayed a circadian rhythm in mouse liver, coincident with that of CENU tolerability, We investigated whether AGT activity displayed a circadian rhythm in human circulating mononuclear cells (MNCs), The study was performed in 12 healthy volunteers aged 19 to 31 years, Circadian synchronization was verified with rest/activity cycle as assessed with wrist actigraphy andplasma cortisol and melatonin rhythms. Subjects were hospitalized for 24 hr and blood samples were obtained at 08:00, 12:00, 16:00, 20:00, 22:00, 00:00, 02:00, 04:00 and 08:00 overnight, MNCs were isolated on Ficoll immediately after blood sampling and frozen at -196 degreesC until AGT activity determination by HPLC, Mean ACT activity(+/- SEM) varied from 82 +/- a 67 fmol/mg of total proteins at noon (trough), up to 1055 +/- 80 fmol/mg at midnight (peak), i.e,, by similar to 30%, A circadian rhythm was statistically validated with both analysis of variance (p < 0.009) and cosinor (p < 0.02) for AGT activity in MNCs (acrophase +/- SD at 00:30 +/- 210 min) as well as for MNC circulating count and for plasma cortisol and melatonin concentrations. Despite individual variations in the extent of AGT activity rhythm (more or less pronounced according to subject), AGT activity displayed a circadian rhythm in human MNCs of our healthy study group subjects. The results warrant to further investigate ACT rhythmicity both in circulating MNCs andin target tissues of cancer patients, as a prerequisite for clinical testing of chronotherapy with alkylating agents. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 04:46:00