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Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points.

Abstract

Although smoking cessation is the primary goal for the control of cancer and other smoking-related diseases, chemoprevention provides a complementary approach applicable to high risk individuals such as current smokers and ex-smokers. The thiol N-acetylcysteine (NAC) works per se in the extracellular environment, and is a precursor of intracellular cysteine and glutathione (GSH). Almost 40 years of experience in the prophylaxis and therapy of a variety of clinical conditions, mostly involving GSH depletion and alterations of the redox status, have established the safety of this drug, even at very high doses and for long-term treatments. A number of studies performed since 1984 have indicated that NAC has the potential to prevent cancer and other mutation-related diseases. N-Acetylcysteine has an impressive array of mechanisms and protective effects towards DNA damage and carcinogenesis, which are related to its nucleophilicity, antioxidant activity, modulation of metabolism, effects in mitochondria, decrease of the biologically effective dose of carcinogens, modulation of DNA repair, inhibition of genotoxicity and cell transformation, modulation of gene expression and signal transduction pathways, regulation of cell survival and apoptosis, anti-inflammatory activity, anti-angiogenetic activity, immunological effects, inhibition of progression to malignancy, influence on cell cycle progression, inhibition of pre-neoplastic and neoplastic lesions, inhibition of invasion and metastasis, and protection towards adverse effects of other chemopreventive agents or chemotherapeutical agents. These mechanisms are herein reviewed and commented on with special reference to smoking-related end-points, as evaluated in in vitro test systems, experimental animals and clinical trials. It is important that all protective effects of NAC were observed under a range of conditions produced by a variety of treatments or imbalances of homeostasis. However, our recent data show that, at least in mouse lung, under physiological conditions NAC does not alter per se the expression of multiple genes detected by cDNA array technology. On the whole, there is overwhelming evidence that NAC has the ability to modulate a variety of DNA damage- and cancer-related end-points.

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  • Authors+Show Affiliations

    ,

    Department of Health Sciences, Section of Hygiene and Preventive Medicine, University of Genoa, Via A. Pastore 1, I-16132 Genoa, Italy. sdf@unige.it

    , ,

    Source

    Carcinogenesis 22:7 2001 Jul pg 999-1013

    MeSH

    Acetylcysteine
    Animals
    Anticarcinogenic Agents
    Antimutagenic Agents
    Humans
    Smoking

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't
    Review

    Language

    eng

    PubMed ID

    11408342

    Citation

    De Flora, S, et al. "Mechanisms of N-acetylcysteine in the Prevention of DNA Damage and Cancer, With Special Reference to Smoking-related End-points." Carcinogenesis, vol. 22, no. 7, 2001, pp. 999-1013.
    De Flora S, Izzotti A, D'Agostini F, et al. Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. Carcinogenesis. 2001;22(7):999-1013.
    De Flora, S., Izzotti, A., D'Agostini, F., & Balansky, R. M. (2001). Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. Carcinogenesis, 22(7), pp. 999-1013.
    De Flora S, et al. Mechanisms of N-acetylcysteine in the Prevention of DNA Damage and Cancer, With Special Reference to Smoking-related End-points. Carcinogenesis. 2001;22(7):999-1013. PubMed PMID: 11408342.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smoking-related end-points. AU - De Flora,S, AU - Izzotti,A, AU - D'Agostini,F, AU - Balansky,R M, PY - 2001/6/16/pubmed PY - 2001/8/3/medline PY - 2001/6/16/entrez SP - 999 EP - 1013 JF - Carcinogenesis JO - Carcinogenesis VL - 22 IS - 7 N2 - Although smoking cessation is the primary goal for the control of cancer and other smoking-related diseases, chemoprevention provides a complementary approach applicable to high risk individuals such as current smokers and ex-smokers. The thiol N-acetylcysteine (NAC) works per se in the extracellular environment, and is a precursor of intracellular cysteine and glutathione (GSH). Almost 40 years of experience in the prophylaxis and therapy of a variety of clinical conditions, mostly involving GSH depletion and alterations of the redox status, have established the safety of this drug, even at very high doses and for long-term treatments. A number of studies performed since 1984 have indicated that NAC has the potential to prevent cancer and other mutation-related diseases. N-Acetylcysteine has an impressive array of mechanisms and protective effects towards DNA damage and carcinogenesis, which are related to its nucleophilicity, antioxidant activity, modulation of metabolism, effects in mitochondria, decrease of the biologically effective dose of carcinogens, modulation of DNA repair, inhibition of genotoxicity and cell transformation, modulation of gene expression and signal transduction pathways, regulation of cell survival and apoptosis, anti-inflammatory activity, anti-angiogenetic activity, immunological effects, inhibition of progression to malignancy, influence on cell cycle progression, inhibition of pre-neoplastic and neoplastic lesions, inhibition of invasion and metastasis, and protection towards adverse effects of other chemopreventive agents or chemotherapeutical agents. These mechanisms are herein reviewed and commented on with special reference to smoking-related end-points, as evaluated in in vitro test systems, experimental animals and clinical trials. It is important that all protective effects of NAC were observed under a range of conditions produced by a variety of treatments or imbalances of homeostasis. However, our recent data show that, at least in mouse lung, under physiological conditions NAC does not alter per se the expression of multiple genes detected by cDNA array technology. On the whole, there is overwhelming evidence that NAC has the ability to modulate a variety of DNA damage- and cancer-related end-points. SN - 0143-3334 UR - https://www.unboundmedicine.com/medline/citation/11408342/full_citation L2 - https://academic.oup.com/carcin/article-lookup/doi/10.1093/carcin/22.7.999 DB - PRIME DP - Unbound Medicine ER -