TY - JOUR
T1 - Preparation, isolation, and characterization of dibenzo[a,l]pyrene diol epoxide-deoxyribonucleoside monophosphate adducts by HPLC and fluorescence line-narrowing spectroscopy
AU - Devanesan, Prabu
AU - Ariese, Freek
AU - Jankowiak, Ryszard
AU - Small, Gerald J.
AU - Rogan, Eleanor G.
AU - Cavalieri, Ercole L.
PY - 1999
Y1 - 1999
N2 - Dibenzo[a,l]pyrene (DB[a,l]P) is the most potent carcinogenic polycyclic aromatic hydrocarbon that has been identified in the environment. Earlier studies in our laboratory indicated that more than 80% of the DB[a,l]P-DNA adducts formed in vitro were depurinating adducts and that most of the stable adducts were formed from diol epoxide intermediates. To complete the profile of both stable and depurinating adducts of DB[a,l]P, we have synthesized standard adducts by reacting 3'-dAMP or 3'-dGMP with either (+)-anti- or (±)-syn-dibenzo[a,l]pyrene 11,12-dihydrodiol 13,14-epoxide (DB[a,l]PDE). The adducts were separated by HPLC with an ion-pair column and were identified by fluorescence line-narrowing spectroscopy (FLNS). A total of six pairs of stereoisomers along with another stable DB[a,l]PDE-DNA adduct were successfully isolated and identified. Pairs of (±)-trans and (±)-cis isomers were expected to be formed from the reaction of anti-DB[a,l]PDE with either dAMP or dGMP. While we were able to identify two pairs of stereoisomeric (±)-syn-DB[a,l]PDE-dAMP (cis and trans) and two pairs of stereoisomeric (±)-anti-DB[a,l]PDE-dAMP (cis and trans) adducts, identification of all the stereoisomers of dGMP adducts proved to be impossible. A pair of (±)-syn-trans-DB[a,l]PDEdGMP adducts, a pair of (±)- anti-cis-DB[a,l]PDE-dGMP adducts, and one syn-cis-DB[a,l]PDEdGMP adduct were conclusively identified by FLNS. These standard adducts will be used to identify the stable DNA adducts formed by DB[a,l]P and DB[a,l]PDE in vitro and in vivo.
AB - Dibenzo[a,l]pyrene (DB[a,l]P) is the most potent carcinogenic polycyclic aromatic hydrocarbon that has been identified in the environment. Earlier studies in our laboratory indicated that more than 80% of the DB[a,l]P-DNA adducts formed in vitro were depurinating adducts and that most of the stable adducts were formed from diol epoxide intermediates. To complete the profile of both stable and depurinating adducts of DB[a,l]P, we have synthesized standard adducts by reacting 3'-dAMP or 3'-dGMP with either (+)-anti- or (±)-syn-dibenzo[a,l]pyrene 11,12-dihydrodiol 13,14-epoxide (DB[a,l]PDE). The adducts were separated by HPLC with an ion-pair column and were identified by fluorescence line-narrowing spectroscopy (FLNS). A total of six pairs of stereoisomers along with another stable DB[a,l]PDE-DNA adduct were successfully isolated and identified. Pairs of (±)-trans and (±)-cis isomers were expected to be formed from the reaction of anti-DB[a,l]PDE with either dAMP or dGMP. While we were able to identify two pairs of stereoisomeric (±)-syn-DB[a,l]PDE-dAMP (cis and trans) and two pairs of stereoisomeric (±)-anti-DB[a,l]PDE-dAMP (cis and trans) adducts, identification of all the stereoisomers of dGMP adducts proved to be impossible. A pair of (±)-syn-trans-DB[a,l]PDEdGMP adducts, a pair of (±)- anti-cis-DB[a,l]PDE-dGMP adducts, and one syn-cis-DB[a,l]PDEdGMP adduct were conclusively identified by FLNS. These standard adducts will be used to identify the stable DNA adducts formed by DB[a,l]P and DB[a,l]PDE in vitro and in vivo.
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U2 - 10.1021/tx980202x
DO - 10.1021/tx980202x
M3 - Article
C2 - 10490499
AN - SCOPUS:0032871770
SN - 0893-228X
VL - 12
SP - 789
EP - 795
JO - Chemical Research in Toxicology
JF - Chemical Research in Toxicology
IS - 9
ER -