Stereoselective release of polycyclic aromatic hydrocarbon-deoxyadenosine adducts from DNA by the 32P postlabeling and deoxyribonuclease I/snake venom phosphodiesterase digestion methods

Journal Article · Thu Nov 01 04:00:00 EST 1990 · Chemical Research in Toxicology; (United States)

DOI:https://doi.org/10.1021/tx00018a009· OSTI ID:5010381

Cheh, A M; Yagi, H; Jerina, D M ^[1]

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1. Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD (United States)

The restricted ability of deoxyribonuclease I/snake venom phosphodiesterase digestion to liberate deoxyadenosine (dA) nucleotide adducts of polycyclic aromatic hydrocarbons from DNA, first observed by Dipple and Pigott with the bay-region diol epoxide adducts of 7,12-dimethylbenz(a)anthracene, has been observed with the dA adducts of benz(a)anthracene and benzo(c)phenanthrene diol epoxides. The micrococcal nuclease/spleen phosphodiesterase digestion used in the original 32P postlabeling procedure developed by Randerath to determine DNA adducts also failed to liberate dA nucleotide adducts quantitatively. Thus either method can potentially lead to an underestimation of the extent to which dA has been modified in DNA. The two digestion procedures exhibit systematic and mostly opposite stereoselectivity in the pattern of which dA adducts are resistant to digestion, which suggest that these adducts may have preferred orientations within modified DNA that are determined by whether they have the R or S configuration at C-1, the point of attachment between the exocyclic amino group of dA and the hydrocarbon; this in turn is dictated by the configuration about the precursor benzylic epoxide carbon and the cis versus trans nature of epoxide opening during adduct formation.

• OSTI ID: 5010381
• Journal Information: Chemical Research in Toxicology; (United States), Journal Name: Chemical Research in Toxicology; (United States) Vol. 3:6; ISSN CRTOE; ISSN 0893-228X
• Country of Publication: United States
• Language: English

Related Subjects

550501 -- Metabolism-- Tracer Techniques
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AROMATICS
BENZANTHRACENE
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOSYNTHESIS
CONDENSED AROMATICS
DAYS LIVING RADIOISOTOPES
DNA ADDUCTS
ENZYME ACTIVITY
ENZYMES
ESTERASES
HYDROCARBONS
HYDROLASES
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
METABOLISM
NUCLEI
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
PHOSPHODIESTERASES
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
RADIOISOTOPES
SYNTHESIS
TRACER TECHNIQUES