Preparation, isolation, and characterization of dibenzo[a,l]pyrene diol epoxide-deoxyribonucleoside monophosphate adducts by HPLC and fluorescence line-narrowing spectroscopy

Prabu Devanesan, Freek Ariese, Ryszard Jankowiak, Gerald J. Small, Eleanor G Rogan, Ercole Cavalieri

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)789-795
Number of pages7
JournalChemical Research in Toxicology
Volume12
Issue number9
DOIs
StatePublished - Oct 5 1999

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Deoxyribonucleosides
DNA Adducts
Spectrum Analysis
Fluorescence
High Pressure Liquid Chromatography
Spectroscopy
Stereoisomerism
Epoxy Compounds
Polycyclic Aromatic Hydrocarbons
Isomers
Ions
2'-deoxyguanosine 5'-phosphate
dibenzo(a,l)pyrene diol epoxide
In Vitro Techniques

ASJC Scopus subject areas

  • Toxicology

Cite this

Preparation, isolation, and characterization of dibenzo[a,l]pyrene diol epoxide-deoxyribonucleoside monophosphate adducts by HPLC and fluorescence line-narrowing spectroscopy. / Devanesan, Prabu; Ariese, Freek; Jankowiak, Ryszard; Small, Gerald J.; Rogan, Eleanor G; Cavalieri, Ercole.

In: Chemical Research in Toxicology, Vol. 12, No. 9, 05.10.1999, p. 789-795.

Research output: Contribution to journalArticle

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abstract = "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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AU - Devanesan, Prabu

AU - Ariese, Freek

AU - Jankowiak, Ryszard

AU - Small, Gerald J.

AU - Rogan, Eleanor G

AU - Cavalieri, Ercole

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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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