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Titolo:
Age-related increases of 8-hydroxy-2 '-deoxyguanosine and DNA-protein crosslinks in mouse organs
Autore:
Izzotti, A; Cartiglia, C; Taningher, M; De Flora, S; Balansky, R;
Indirizzi:
Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy Univ Genoa Genoa Italy I-16132 enoa, Dept Hlth Sci, I-16132 Genoa, Italy Univ Genoa, IST, Dept Oncol Biol & Genet, Genoa, Italy Univ Genoa Genoa Italy enoa, IST, Dept Oncol Biol & Genet, Genoa, Italy Natl Oncol Ctr, BU-1157 Sofia, Bulgaria Natl Oncol Ctr Sofia Bulgaria BU-1157 Oncol Ctr, BU-1157 Sofia, Bulgaria
Titolo Testata:
MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS
fascicolo: 2, volume: 446, anno: 1999,
pagine: 215 - 223
SICI:
1383-5718(199912)446:2<215:AIO8'A>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
OXIDATIVE DAMAGE; N-ACETYLCYSTEINE; I-COMPOUNDS; RAT-BRAIN; ADDUCTS; LINKS; ASSAY; LIVER; LUNG; CHEMOPREVENTION;
Keywords:
aging; oxidative DNA damage; DNA-protein crosslinks; 8-hydroxy-2 '-deoxyguanosine; P-32 postlabelling;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: De Flora, S Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy Univ Genoa Via A Pastore 1 Genoa Italy I-16132 2 Genoa, Italy
Citazione:
A. Izzotti et al., "Age-related increases of 8-hydroxy-2 '-deoxyguanosine and DNA-protein crosslinks in mouse organs", MUT RES-GTE, 446(2), 1999, pp. 215-223

Abstract

Experimental data suggest a possible role of DNA damage in aging, mainly related to oxidative lesions. With the objective of evaluating DNA lesions as molecular biomarkers of aging, we measured 8-hydroxy-2'-deoxyguanosine (8-OH-dG) and DNA-protein crosslinks (DPXL) levels in different organs of mice aged 12 and 24 months. 8-OH-dG was detected by P-32 postlabelling after removing unmodified dG by trifluoracetic acid, which prevented the artificial formation of 8-OH-dG during P-32 labelling procedures. Appreciable 8-OH-dG amounts were detected in 12-month-old mice in liver (1.8 +/- 0.7 8-OH-dG/10(5) normal nucleotides), brain (1.6 +/- 0.5) and heart (2.3 +/- 0.5). In 24-month-old mice these values were higher in all examined organs (liver, 2.7 +/- 0.4; brain, 3.6 +/- 1.1; heart, 6.8 +/- 2.2 8-OH-dG/10(5) normal nucleotides). This accounted for a 1.5-fold increase in liver (not significant), 2.3-fold increase in brain (P < 0.01), and 3.0-fold increase in heart(P < 0.001). A similar trend was observed for DPXL levels, which were the 1.8 /- 0.3%, 1.2 +/- 0.2%, and 2.2 +/- 0.3% of total DNA in liver, brain, and heart of 12-month-old mice and 1.9 +/- 0.4%, 2.0 +/- 0.4%, and 3.4 +/- 0.5%in 24-month-old mice, with ratios of 1.0, 1.7 (P < 0.01), and 1.5 (P < 0.001), respectively. Highly significant correlations between 8-OH-dG and DPXLlevels were recorded in brain (r = 0.619, P < 0.001) and heart (r = 0.800,P < 0.0001), but not in liver (r = 0.201, not significant). These data suggest that brain and heart are more severely affected by the monitored age-related DNA lesions than liver, which can be ascribed to certain characteristics of these postmitotic organs, including the low detoxifying capacities,the high oxygen consumption, and the impossibility to replace damaged cells by mitosis. The strong correlation between 8-OH-dG and DPXL supports a possible contribution of oxidative mechanisms to formation of DPXL in those organs, such as brain and heart, which play a primary role in the aging of the whole organism. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/07/20 alle ore 07:14:12