Studies of the mechanisms of adduction of 2'-deoxyadenosine with styrene oxide and polycyclic aromatic hydrocarbon dihydrodiol epoxides.
The mechanism of adduction of 2'-deoxyadenosine by styrene oxide and polycyclic aromatic hydrocarbon dihydrodiol epoxides has been explored using (15)N(6)-labeled adenine nucleosides. The extent of reaction at N1 versus N(6) was evaluated by (1)H NMR of the N(6) adducts after allowing Dimroth rearrangement to occur. Products arising from attack at N1 followed by Dimroth rearrangement exhibited a small two-bond (1)H-(15)N coupling constant (N1-H2 J approximately 13 Hz); products from direct attack exhibited a much larger one-bond (1)H-(15)N coupling constant (J approximately 90 Hz). In the case of styrene oxide, all of the N(6) beta adduct arose by initial attack at N1, whereas the majority (70-80%) of the N(6) alpha adducts came from direct attack. The styrene oxide reaction was also studied with a self-complementary oligodeoxynucleotide (24-mer) containing nine (15)N(6)-labeled adenine residues. NMR examination of the N(6) alpha- and beta-styrene oxide adducts isolated after enzymatic degradation of the 24-mer gave very similar results, indicating that N1 attack can occur readily even with a duplexed oligonucleotide. With the PAH dihydrodiol epoxides, only naphthalene dihydrodiol epoxide exhibited significant initial reaction at N1 (50%). No detectable rearranged product was seen in reactions with benzo[a]pyrene dihydrodiol epoxide or non-bay or bay region benz[a]anthracene dihydrodiol epoxide; interestingly, a small amount of N1 attack (5-7%) was seen in the case of benzo[c]phenanthrene dihydrodiol epoxide. It appears that initial attack at N1 is only a significant reaction pathway for epoxides attached to a single aromatic ring.
Kim
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Chemistry Department and Center in Molecular Toxicology, Vanderbilt University, Nashville, TN 37235, USA.
Finneman
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Harris
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Harris
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D001483:Base Sequence; D002273:Carcinogens / Q000737:chemistry; D018736:DNA Adducts / Q000032:analysis* / Q000737:chemistry; D003839:Deoxyadenosines / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009587:Nitrogen Isotopes / Q000032:analysis; D009841:Oligonucleotides / Q000737:chemistry; D010616:Phenanthrenes / Q000737:chemistry*
D002273:Carcinogens; D018736:DNA Adducts; D003839:Deoxyadenosines; D004852:Epoxy Compounds; D009587:Nitrogen Isotopes; D009841:Oligonucleotides; D010616:Phenanthrenes; C013690:styrene oxide; C058118:2'-deoxyadenosine