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Titolo:
N-acetylcysteine, a cancer chemopreventive agent, causes oxidative damage to cellular and isolated DNA
Autore:
Oikawa, S; Yamada, K; Yamashita, N; Tada-Oikawa, S; Kawanishi, S;
Indirizzi:
Mie Univ, Sch Med, Dept Hyg, Tsu, Mie 514, Japan Mie Univ Tsu Mie Japan 514 e Univ, Sch Med, Dept Hyg, Tsu, Mie 514, Japan
Titolo Testata:
CARCINOGENESIS
fascicolo: 8, volume: 20, anno: 1999,
pagine: 1485 - 1490
SICI:
0143-3334(199908)20:8<1485:NACCAC>2.0.ZU;2-E
Fonte:
ISI
Lingua:
ENG
Soggetto:
HYDROGEN-PEROXIDE; VITAMIN-E; RATS; INDUCTION; COPPER; SITE; MECHANISMS; PREVENTION; CLEAVAGE; IONS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Kawanishi, S Mie Univ, Sch Med, Dept Hyg, Tsu, Mie 514, Japan Mie Univ Tsu Mie Japan 514 ed, Dept Hyg, Tsu, Mie 514, Japan
Citazione:
S. Oikawa et al., "N-acetylcysteine, a cancer chemopreventive agent, causes oxidative damage to cellular and isolated DNA", CARCINOGENE, 20(8), 1999, pp. 1485-1490

Abstract

Although N-acetylcysteine is an antioxidant which has been expected to be a cancer chemopreventive agent, its safety and risk assessment have not been evaluated. N-acetylcysteine increased the amount of 8-oxo-7,8-dihydro-2 'deoxyguanosine (8-oxodG), a characteristic oxidative DNA lesion, in human leukemia cell line HL-60, whereas the amount of 8-oxodG in HP100, which is ahydrogen peroxide (H2O2)-resistant cell line derived from HL-60, was not increased. To clarify the mechanism of cellular DNA damage, we investigated DNA damage and its site specificity induced by N-acetylcysteine, using P-32-labeled DNA fragments obtained from the human p53 tumor suppressor gene and the c-Ha-ras-l protooncogene. N-acetylcysteine induced extensive DNA damage in the presence of Cu(II), The DNA cleavage was enhanced by piperidine treatment, suggesting that N-acetylcysteine plus Cu(II) caused not only deoxyribose phosphate backbone breakage but also base modification. N-acetylcysteine plus Cu(II) frequently modified thymine and guanine residues. Bathocuproine, a specific Cu(I) chelator, and catalase inhibited the DNA damage, indicating the participation of Cu(I) and H2O2 in the DNA damage, Typical hydroxyl radical scavengers did not inhibit N-acetylcysteine plus Cu(II)-induced DNA damage, whereas methional completely inhibited it. These results suggest that reactive species derived from the reaction of H2O2 with Cu(I) participates in N-acetylcysteine plus Cu(II)-induced DNA damage. The content of 8-oxodG in calf thymus DNA was increased by N-acetylcysteine in the presence of Cu(II), The present study has demonstrated that N-acetylcysteine could induce metal-dependent H2O2 generation and, subsequently, damage to cellular and isolated DNA, Therefore, it is reasonable to consider that N-acetylcysteine may have the dual function of carcinogenic and anti-carcinogenicpotentials. This work requires further studies on safety and risk assessment of N-acetylcysteine.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 16/07/20 alle ore 19:57:06