Related Experiment Video
Updated: Jun 4, 2026
09:33
Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
Benzene induces cytotoxicity without metabolic activation
Takuro Nishikawa1, Kimiko Izumo, Emiko Miyahara
1Department of Environmental Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Japan.
Journal of Occupational Health
|February 18, 2011
Summary
Benzene exposure causes cell death and oxidative stress in human myeloid cells, independent of its metabolism. Further research is needed to understand benzene
Area of Science:
- Toxicology
- Hematology
- Molecular Biology
Background:
- Benzene is linked to hematological disorders like leukemia and aplastic anemia.
- Benzene metabolites cause toxicity via reactive oxygen species (ROS), topoisomerase inhibition, and DNA damage.
- Benzene itself is generally considered non-mutagenic and non-cytotoxic.
Purpose of the Study:
- To investigate the direct effects of benzene on a human myeloid cell line.
- To determine if benzene's cytotoxicity is mediated by its metabolites.
- To assess benzene's impact on DNA methylation, apoptosis, and ROS production.
Main Methods:
- HL-60 cells were exposed to benzene.
- Benzene metabolizing enzyme inhibitors (cytochrome P450 2E1 and myeloperoxidase inhibitors) were used.
- Cytotoxicity was measured by global DNA methylation, apoptosis induction, and ROS production.
Main Results:
- Benzene exposure did not alter global DNA methylation levels.
- Benzene significantly increased apoptosis and ROS production in HL-60 cells.
- Inhibiting benzene metabolism did not affect benzene's cytotoxic effects or ROS induction.
- Benzene increased mRNA levels of oxidative stress genes and activator protein-1.
Conclusions:
- Benzene exhibits direct cytotoxic effects on human myeloid cells, independent of its metabolism.
- Benzene influences gene expression related to oxidative stress.
- Investigating both benzene and its metabolites is crucial for understanding its toxicity mechanisms.
More Related Videos
Related Concept Videos
01:25Bioactivation and Tissue Toxicity
Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
00:59Reactions at the Benzylic Position: Oxidation and Reduction
The benzylic position describes the position of a carbon atom attached directly to a benzene ring. Benzene by itself does not undergo oxidation. In contrast, the benzylic carbon is quite reactive in the presence of strong oxidizing agents such as KMnO4 or H2CrO4. Therefore, alkylbenzenes are readily oxidized to benzoic acid, irrespective of the type of alkyl groups.
01:28Reduction of Benzene to Cyclohexane: Catalytic Hydrogenation
Unlike the easy catalytic hydrogenation of an alkene double bond, hydrogenation of a benzene double bond under similar reaction conditions does not take place easily. For example, in the reduction of stilbene, the benzene ring remains unaffected while the alkene bond gets reduced. Hydrogenation of an alkene double bond is exothermic and a favorable process. In contrast, to hydrogenate the first unsaturated bond of benzene, an energy input is needed; that is, the process is endothermic. This is...
01:07Structure of Benzene: Kekulé Model
In 1865, August Kekule suggested the structure of benzene according to the structural theory of organic chemistry based on the three assertions—formula of benzene is C6H6, all the hydrogens of benzene are equivalent, and each carbon must have four bonds due to its tetravalency.
He proposed that benzene has a cyclic structure of six carbon atoms attached to one hydrogen atom each, with three alternating pi bonds.
He proposed that benzene has a cyclic structure of six carbon atoms attached to one hydrogen atom each, with three alternating pi bonds.
01:22Electrophilic Aromatic Substitution: Sulfonation of Benzene
Sulfonation of benzene is a reaction wherein benzene is treated with fuming sulfuric acid at room temperature to produce benzenesulfonic acid. Fuming sulfuric acid is a mixture of sulfur trioxide and concentrated sulfuric acid.
01:11Nucleophilic Aromatic Substitution: Elimination–Addition
Simple aryl halides do not react with nucleophiles. However, nucleophilic aromatic substitutions can be forced under certain conditions, such as high temperatures or strong bases. The mechanism of substitution under such conditions involves the highly unstable and reactive benzyne intermediate. Benzyne contains equivalent carbon centers at both ends of the triple bond, each of which is equally susceptible to nucleophilic attack. This 50–50 distribution of products is confirmed through isotopic...