The genotoxicity and carcinogenicity of paracetamol: a regulatory (re) view

Bergman, Kerstin; Müller, Lutz; Sw, Teigen

doi:10.1016/0027-5107(95)00185-9

Cited by 101 publications

(56 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For instances, colleagues (1983 and1985) reported that APAP can increase the mutation rates through oxidative damage. In contrast, many other reports suggest that APAP is considered safe and non-mutagenic (for a review, see Bergman et al, 1996). These conflicting reports may derive from differences in: experimental models, route and dose of APAP administration, pre-existing conditions of host cells or animals, target tissues examined, etc.…”

Section: Discussionmentioning

confidence: 58%

Acetoaminophen-induced accumulation of 8-oxodeoxyguanosine through reduction of Ogg1 DNA repair enzyme in C6 glioma cells

Wan

Bae²,

Song³

2004

Exp Mol Med

View full text Add to dashboard Cite

A bstractLarge doses of acetam inophen (APAP) could cause oxidative stress and tissue dam age through production of reactive oxygen/nitrogen (RO S/RNS) species and quinone m etabolites of APAP. Although ROS/RNS are know n to m odify DNA, the effect of APAP on DNA m odifications has not been studied system atically. In this study, w e investigate whether large doses of APAP can m odify the nuclear DNA in C6 gliom a cells used as a m odel system , because these cells contain cytochrom e P450-related enzym es responsible for APAP m etabolism and subsequent toxicity (G eng and Strobel, 1995). O ur results revealed that APAP produced RO S and significantly elevated the 8-oxodeoxyguanosine (8-oxodG) levels in the nucleus of C6 gliom a cells in a tim e and concentration dependent m anner. APAP significantly reduced the 8-oxodG incision activity in the nucleus by decreasing the activity and content of a DNA repair enzym e, O gg1. These results indicate that APAP in large doses can increase the 8-oxodG level partly through significant reduction of O gg1 DNA repair enzym e.

show abstract

Section: Discussionmentioning

confidence: 58%

Acetoaminophen-induced accumulation of 8-oxodeoxyguanosine through reduction of Ogg1 DNA repair enzyme in C6 glioma cells

Wan

Bae²,

Song³

2004

Exp Mol Med

View full text Add to dashboard Cite

show abstract

“…However, in conditions where the production of NAPQI exceeds that of glutathione, this reactive metabolite binds covalently to liver proteins and causes dose-related liver injury by centrilobular necrosis [5,6].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and pharmacological evaluation of N-phenyl-acetamide sulfonamides designed as novel non-hepatotoxic analgesic candidates

Barbosa

Melo

Silva

et al. 2009

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

“…Acetaminophen, on the other hand, is devoid of any carcinogenicity risks at therapeutic doses and quickly replaced phenacetin. It is currently one of the most popular analgesics in the market [43,44]. Likewise, desvenlafaxine (Pristiq), which was developed as a serotonin norepinephrine reuptake inhibitor (SNRIs) in the treatment of depression, is a major active O-dealkylated metabolite of venlafaxine (Effexor) (Fig.…”

Section: Dealkylationmentioning

confidence: 99%

Bioactivation I: Bioactivation by Cytochrome P450s

Dalvie

2012

Encyclopedia of Drug Metabolism and Interactions

View full text Add to dashboard Cite

Metabolism reactions generally result in detoxification of xenobiotics and are accompanied by the formation of chemically stable metabolites, which are devoid of pharmacological or toxicological activities. However, in some cases, these reactions can convert drugs to products that are either chemically reactive or pharmacologically active, a process that is commonly referred to as metabolic activation or bioactivation . Most, if not all, functionalization and conjugation reactions can result in bioactivation. Even though all enzymes have the propensity to catalyze the metabolic activation of compounds, cytochrome P450 (P450) enzymes, which generally dominate metabolism, play a major role in the metabolic activation of drugs. The primary objective of this chapter is to provide an overview of bioactivation by P450 to pharmacologically active and chemically reactive metabolites. The common reactions that result in bioactivation of xenobiotics and consequences of bioactivation have been discussed here.

show abstract

The genotoxicity and carcinogenicity of paracetamol: a regulatory (re) view

Cited by 101 publications

References 81 publications

Acetoaminophen-induced accumulation of 8-oxodeoxyguanosine through reduction of Ogg1 DNA repair enzyme in C6 glioma cells

Acetoaminophen-induced accumulation of 8-oxodeoxyguanosine through reduction of Ogg1 DNA repair enzyme in C6 glioma cells

Synthesis and pharmacological evaluation of N-phenyl-acetamide sulfonamides designed as novel non-hepatotoxic analgesic candidates

Bioactivation I: Bioactivation by Cytochrome P450s

Contact Info

Product

Resources

About