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Titolo:
CHEMOPREVENTIVE PROPERTIES AND MECHANISMS OF N-ACETYLCYSTEINE - THE EXPERIMENTAL BACKGROUND
Autore:
DEFLORA S; CESARONE CF; BALANSKY RM; ALBINI A; DAGOSTINI F; BENNICELLI C; BAGNASCO M; CAMOIRANO A; SCATOLINI L; ROVIDA A; IZZOTTI A;
Indirizzi:
UNIV GENOA,INST HYG & PREVENT MED,VIA PASTORE 1 I-16132 GENOA ITALY UNIV GENOA,INST GEN PHYSIOL I-16132 GENOA ITALY NATL ONCOL CTR BU-1756 SOFIA BULGARIA NATL INST CANC RES I-16132 GENOA ITALY
Titolo Testata:
Journal of cellular biochemistry
, , anno: 1995, supplemento:, 22
pagine: 33 - 41
SICI:
0730-2312(1995):<33:CPAMON>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
ALVEOLAR MACROPHAGES; CIGARETTE-SMOKE; DNA ADDUCTS; RAT LUNG; MUTAGENICITY; INHIBITION; DEPLETION; EXPOSURE; LIVER;
Keywords:
N-ACETYLCYSTEINE; ANTICARCINOGENICITY; ANTIMUTAGENICITY; ANTIOXIDANTS; GLUTATHIONE; MOLECULAR DOSIMETRY; THIOLS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
S. Deflora et al., "CHEMOPREVENTIVE PROPERTIES AND MECHANISMS OF N-ACETYLCYSTEINE - THE EXPERIMENTAL BACKGROUND", Journal of cellular biochemistry, 1995, pp. 33-41

Abstract

The thiol N-acetylcysteine (NAG), now under clinical trial for cancerchemoprevention both in Europe (project Euroscan) and in the US (National Cancer Institute), has been shown during the past decade to exertprotective effects in a variety of experimental test systems. NAC inhibited spontaneous mutagenicity and that induced by a number of chemical compounds and complex mixtures. Moreover, NAC significantly decreased the incidence of neoplastic and preneoplastic lesions induced by several chemical carcinogens in rodents (mice, rats, hamsters), e.g., inlung, trachea, colon, liver, mammary gland, Zymbal gland, bladder andskin. Our studies provided evidence that multiple mechanisms contribute to NAC antimutagenicity and anticarcinogenicity. They include extracellular mechanisms, such as detoxification of reactive compounds due to the nucleophilic and antioxidant properties of NAG, inhibition of nitrosation products, and enhancement of thiol concentration in intestinal bacteria; trapping and enhanced detoxification of carcinogens in long-lived non-target cells, such as erythrocytes and bronchoalveolar lavage cells; mechanisms working in the cytoplasm of target cells, suchas replenishment of GSH stores, modulation of metabolism of mutagens/carcinogens, blocking of electrophiles, and scavenging of reactive oxygen species; and nuclear effects, such as inhibition of DNA adduction by metabolites of carcinogens, inhibition of ''spontaneous'' mutations, attenuation of carcinogen-induced DNA damage, and protection of nuclear enzymes, such as poly(ADP-ribose) polymerase. In particular, benzo(a)pyrene diolepoxide-DNA adducts in rats exposed either to benzo(a)pyrene or cigarette smoke were prevented by NAC not only in target organs far carcinogenicity, such as lung and trachea, but also in other organs, such as heart, aorta and testis, where these molecular biomarkershave been tentatively associated with cardiomyopathies, atherosclerosis and hereditary diseases, respectively. The protective mechanisms ofNAC are expected to affect not only initiation but also promotion andprogression, due to the reiterate involvement of: certain key mechanisms in carcinogenesis. Moreover, recent studies demonstrate that NAC can also affect the steps of invasion and metastasis, including the specific inhibition of type TV collagenases degrading basement membranes,inhibition of chemotactic and invasive activities of human and murinemalignant cells, delay of primary tumor formation in mice, and inhibition of lung metastases. Evidence was also provided that administration of pharmacological doses of NAC sharply decreases urinary excretion of mutagens in smokers. (C) 1995 Wiley-Liss, Inc.

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Documento generato il 21/09/20 alle ore 00:47:34