Formation of cyclic 1,N2-propanodeoxyguanosine and thymidine adducts in the reaction of the mutagen 2-bromoacrolein with calf thymus DNA
- Univ. of Leiden (Netherlands)
The interaction of the mutagen 2-bromoacrolein (2BA) with DNA and thymidine was studied in vitro by reaction of (3-3H)2BA with thymidine, RNA, single-stranded DNA, and double-stranded DNA in phosphate buffer (pH 7.4). After purification of the nucleic acids, they were incubated at alkaline pH to convert any (hydroxybromo)propano(deoxy)-guanosine adducts to their dihydroxy analogues. After acid or enzymatic hydrolysis, the hydrolysates were analyzed by reversed-phase high-performance liquid chromatography. At a concentration of 1.6 mM, the fraction of 2BA that became covalently bound to DNA was 2.3% of the amount added. Only 3% of the radioactivity bound to DNA after extensive purification could be accounted for as cyclic 1,N2-(6,7-dihydroxy)-propanoguanine adducts. More 2BA became covalently bound to single-stranded DNA and RNA as compared with double-stranded DNA. However, high-performance liquid chromatographic analyses showed that formation of cyclic 1,N2-(6,7-dihydroxy)propanoguanine adducts was also a minor reaction with these macromolecules. Because these data showed that other type(s) of reaction(s) are more important in the reaction of 2BA with nucleic acids, we have investigated the reaction of 2BA with other nucleosides. It was found that 2BA reacted well with thymidine in vitro, and the major product was identified by 500 MHz 1H and 75.43 MHz 13C nuclear magnetic resonance and thermospray mass spectrometry as 3-(2-bromo-3-oxopropyl)thymidine. This adduct was unstable and decomposed upon storage. After enzymatic hydrolysis of (3H)2BA-modified double-stranded DNA and subsequent analysis of the hydrolysate by high-performance liquid chromatography, 22% of the covalently bound radioactivity to DNA coeluted with decomposition products of the 3-(bromooxypropyl)thymidine adduct.
- OSTI ID:
- 5023771
- Journal Information:
- Cancer Research; (USA), Vol. 49:22; ISSN 0008-5472
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ACROLEIN
METABOLISM
DNA ADDUCTS
BIOSYNTHESIS
CALVES
CARBON 13
DNA
ENZYMATIC HYDROLYSIS
FRACTIONATION
IN VITRO
LIQUID COLUMN CHROMATOGRAPHY
LIVER
MASS SPECTROSCOPY
MOLECULAR STRUCTURE
MUTAGENS
NUCLEAR MAGNETIC RESONANCE
RATS
REAGENTS
RNA
THYMIDINE
THYMUS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ADDUCTS
ALDEHYDES
ANIMALS
AZINES
BODY
CARBON ISOTOPES
CATTLE
CHEMICAL REACTIONS
CHROMATOGRAPHY
DECOMPOSITION
DIGESTIVE SYSTEM
DOMESTIC ANIMALS
EVEN-ODD NUCLEI
GLANDS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROLYSIS
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LYMPHATIC SYSTEM
LYSIS
MAGNETIC RESONANCE
MAMMALS
NUCLEI
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PYRIMIDINES
RESONANCE
RIBOSIDES
RODENTS
RUMINANTS
SEPARATION PROCESSES
SOLVOLYSIS
SPECTROSCOPY
STABLE ISOTOPES
SYNTHESIS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology
550501 - Metabolism- Tracer Techniques