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Chemopreventive properties and mechanisms of N-Acetylcysteine. The experimental background
- Source :
- Europe PubMed Central
- Publication Year :
- 1995
- Publisher :
- John Wiley & Sons Incorporated:Customer Service, 111 River Street:Hoboken, NJ 07030:(800)225-5945, (201)748-6000, EMAIL: societyinfo@wiley.com, INTERNET: http://www.wiley.com, Fax: (212)748-6551, 1995.
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Abstract
- The thiol N-acetylcysteine (NAC), now under clinical trial for cancer chemoprevention both in Europe (project Euroscan) and in the US (National Cancer Institute), has been shown during the past decade to exert protective 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., in lung, trachea, colon, liver, mammary gland, Zymbal gland, bladder and skin. 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 NAC, 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, such as 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.(ABSTRACT TRUNCATED AT 250 WORDS)
- Subjects :
- Cytoplasm
Antioxidant
DNA damage
medicine.medical_treatment
Pharmacology
Biochemistry
Acetylcysteine
chemistry.chemical_compound
Mice
Cricetinae
medicine
Extracellular
Animals
Anticarcinogenic Agents
Humans
Neoplasm Invasiveness
Neoplasm Metastasis
Molecular Biology
Carcinogen
chemistry.chemical_classification
Reactive oxygen species
Chemistry
Mutagenicity Tests
Cell Biology
Glutathione
Rats
Nitrosation
Inactivation, Metabolic
Biomarkers
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Europe PubMed Central
- Accession number :
- edsair.doi.dedup.....16876dcf1a571e398b306fd7d7ea5c07