Biomaterial Database

Role of the benzoyloxyl radical in DNA damage mediated by benzoyl peroxide. 1991

J E Swauger, and P M Dolan, and J L Zweier, and P Kuppusamy, and T W Kensler

Department of Environmental Health Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.

Benzoyl peroxide (BzPO) is both a tumor promoter and progressor in mouse skin; however, BzPO is neither an initiator nor a complete carcinogen in this tissue. Although not mutagenic, BzPO has been observed to produce strand breaks in DNA of exposed cells. These actions are presumed to be mediated by free-radical derivatives of BzPO. Previous studies suggested that the metabolism of BzPO in keratinocytes proceeds via the initial cleavage of the peroxide bond, yielding benzoyloxy radicals which, in turn, can either fragment to form phenyl radicals and carbon dioxide or abstract H atoms from biomolecules to yield benzoic acid. Benzoic acid is the major stable metabolite of BzPO produced by keratinocytes. In the present study we have investigated the role of BzPO and its metabolites in the generation of strand scissions in a cell-free system using phi X-174 plasmid DNA. In this system BzPO produced DNA damage that was dose-dependent over a concentration range of 0.1-1 mM and required the presence of copper but not other transition metals. By contrast, benoic acid did not produce DNA damage in this system, either in the presence or in the absence of copper. The inclusion of spin trapping agents, such as N-tert-butyl-alpha-phenylnitrone (PBN), 3,5-dibromo-4-nitrosobenzenesulfonate, and nitrosobenzene, in incubations was found to significantly reduce the extent of DNA damage generated via the copper-mediated activation of BzPO. Electron paramagnetic resonance spectroscopy studies suggested that the primary radical trapped by PBN following copper-mediated decomposition of BzPO was the benzoyloxy radical.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D010957	Plasmids	Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.	Episomes,Episome,Plasmid
D003300	Copper	A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.	Copper-63,Copper 63
D004249	DNA Damage	Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.	DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004270	DNA, Circular	Any of the covalently closed DNA molecules found in bacteria, many viruses, mitochondria, plastids, and plasmids. Small, polydisperse circular DNA's have also been observed in a number of eukaryotic organisms and are suggested to have homology with chromosomal DNA and the capacity to be inserted into, and excised from, chromosomal DNA. It is a fragment of DNA formed by a process of looping out and deletion, containing a constant region of the mu heavy chain and the 3'-part of the mu switch region. Circular DNA is a normal product of rearrangement among gene segments encoding the variable regions of immunoglobulin light and heavy chains, as well as the T-cell receptor. (Riger et al., Glossary of Genetics, 5th ed & Segen, Dictionary of Modern Medicine, 1992)	Circular DNA,Circular DNAs,DNAs, Circular
D004278	DNA, Superhelical	Circular duplex DNA isolated from viruses, bacteria and mitochondria in supercoiled or supertwisted form. This superhelical DNA is endowed with free energy. During transcription, the magnitude of RNA initiation is proportional to the DNA superhelicity.	DNA, Supercoiled,DNA, Supertwisted,Supercoiled DNA,Superhelical DNA,Supertwisted DNA
D004305	Dose-Response Relationship, Drug	The relationship between the dose of an administered drug and the response of the organism to the drug.	Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005609	Free Radicals	Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated.	Free Radical
D001585	Benzoyl Peroxide	A peroxide derivative that has been used topically for BURNS and as a dermatologic agent in the treatment of ACNE and POISON IVY DERMATITIS. It is used also as a bleach in the food industry.	Benzoyl Superoxide,Dibenzoyl Peroxide,Diphenylglyoxal Superoxide,PanOxyl,Peroxide, Benzoyl,Peroxide, Dibenzoyl,Superoxide, Benzoyl,Superoxide, Diphenylglyoxal
D001711	Biotransformation	The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.