Biomaterial Database

Formation and accumulation of DNA ethenobases in adult Sprague-Dawley rats exposed to vinyl chloride. 1996

Y Guichard, and F el Ghissassi, and J Nair, and H Bartsch, and A Barbin

International Agency for Research on Cancer, Lyon, France.

DNA ethenobases are promutagenic lesions formed by carcinogens such as vinyl chloride (VC). Their formation was investigated in 6-week old, male Sprague-Dawley rats exposed to 500 p.p.m. VC by inhalation (4 h/day, 5 days/ week) for 1, 2, 4 or 8 weeks and in 7- and 14-week old, matched control animals. 1,N6-Ethenoadenine (epsilon A) and 3, N4-ethenocytosine (epsilon C) deoxyribonucleotides were analysed by immunoaffinity purification and 32P-postlabelling. This postlabelling method was compared with a radio-immunoassay method, which yielded similar results. Background levels of ethenobases were found in DNA from the liver, lungs, kidneys and circulating lymphocytes of unexposed, control rats. In the liver, the following background molar ratios of ethenobase to parent base in DNA were detected (mean values x 10(-8)): epsilon A/A, 0.04-0.05; epsilon C/C, 0.06-0.07. In the lungs, kidneys and circulating lymphocytes, background levels of epsilon A and epsilon C ranged from 1.7 to 4.2 x 10(-8) and from 4.8 to 11.2 x 10(-8), respectively. Following a 5-day exposure to VC, a significant increase of epsilon A and epsilon C was measured in hepatic DNA from rats sacrificed immediately after treatment. Further, a dose-dependent increase of both etheno adducts was observed in liver DNA of VC-treated rats. Compared to the 5-day exposure, approximately 4-fold higher levels of epsilon A and epsilon C were observed in the liver of animals after 8 weeks of exposure. In contrast, there was an accumulation of epsilon C but not of epsilon A in lungs and kidneys. In circulating lymphocytes, no significant increase of ethenobase levels above control values was observed after 2 months of exposure to VC. Both etheno adducts were found to be persistent in liver DNA, after 2 months following the termination of VC exposure. These results further support the notion that DNA etheno-bases are critical lesions in VC-induced carcinogenesis. The possible contribution of lipid peroxidation products that also yield ethenobases, on the formation and persistence of these DNA adducts, remains to be clarified.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D009943	Organophosphorus Compounds	Organic compounds that contain phosphorus as an integral part of the molecule. Included under this heading is broad array of synthetic compounds that are used as PESTICIDES and DRUGS.	Organophosphorus Compound,Organopyrophosphorus Compound,Organopyrophosphorus Compounds,Compound, Organophosphorus,Compound, Organopyrophosphorus,Compounds, Organophosphorus,Compounds, Organopyrophosphorus
D010761	Phosphorus Radioisotopes	Unstable isotopes of phosphorus that decay or disintegrate emitting radiation. P atoms with atomic weights 28-34 except 31 are radioactive phosphorus isotopes.	Radioisotopes, Phosphorus
D002846	Chromatography, Affinity	A chromatographic technique that utilizes the ability of biological molecules, often ANTIBODIES, to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)	Chromatography, Bioaffinity,Immunochromatography,Affinity Chromatography,Bioaffinity Chromatography
D003839	Deoxyadenosines	Adenosine molecules which can be substituted in any position, but are lacking one hydroxyl group in the ribose part of the molecule.	Adenine Deoxyribonucleosides,Adenylyldeoxyribonucleosides,Deoxyadenosine Derivatives,Deoxyribonucleosides, Adenine,Derivatives, Deoxyadenosine
D003841	Deoxycytidine	A nucleoside component of DNA composed of CYTOSINE and DEOXYRIBOSE.	Cytosine Deoxyribonucleoside,Cytosine Deoxyriboside,Deoxyribonucleoside, Cytosine,Deoxyriboside, Cytosine
D004247	DNA	A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).	DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
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
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014752	Vinyl Chloride	A gas that has been used as an aerosol propellant and is the starting material for polyvinyl resins. Toxicity studies have shown various adverse effects, particularly the occurrence of liver neoplasms.	Chloroethylene,Chloride, Vinyl