Determination of benzo[a]pyrene- and 7,12-dimethylbenz[a]anthracene-DNA adducts formed in rat mammary glands

Rosa Todorovic, Freek Ariese, Prabhakar Devanesan, Ryszard Jankowiak, Gerald J. Small, Eleanor G Rogan, Ercole Cavalieri

Research output: Contribution to journalArticle

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Abstract

Both 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (BP) are carcinogenic in the rat mammary gland. The depurinating and stable adducts of DMBA and BP formed in vitro and in mouse skin were previously identified and quantitated. Identification and quantitation of the depurinating and stable DNA adducts of DMBA and identification of the depurinating adducts of BP formed in rat mammary glands in the 24 h after intramammillary injection of DMBA or BP are reported in this paper. The depurinating adducts of DMBA, which constitute 52% of all adducts detected, are DMBA bound at the 12- methyl group to the N-7 of adenine (Ade) or guanine (Gua), namely, 7- methylbenz[a]anthracene (MBA)-12-CH2-N7Ade (39%) and 7-MBA-12-CH2-N7Gua (13%). All of the stable adducts were formed from the diol epoxide(s) of DMBA. Depurinating adducts of BP with guanine, namely, 8-(BP-6-yl)-guanine (BP-6-C8Gua) and BP-6-N7Gua, were identified in rat mammary glands treated with BP. The major stable adduct, formed via the diol epoxide pathway, BP- diol epoxide-10-N2dG, accounted for over 64% of all the stable adducts. Three other BP-DNA stable adducts remain unidentified. Thus, rat mammary cells form depurinating adducts of DMBA and BP predominantly via their radical cations and stable adducts via the diol epoxides.

Original languageEnglish (US)
Pages (from-to)941-947
Number of pages7
JournalChemical Research in Toxicology
Volume10
Issue number9
DOIs
StatePublished - Sep 1 1997

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9,10-Dimethyl-1,2-benzanthracene
Benzo(a)pyrene
Human Mammary Glands
Rats
Epoxy Compounds
Guanine
DNA Adducts
Adenine
7,12-dimethylbenz(a)anthracene-DNA adduct
Cations
Skin
Breast
Injections
DNA

ASJC Scopus subject areas

  • Toxicology

Cite this

Determination of benzo[a]pyrene- and 7,12-dimethylbenz[a]anthracene-DNA adducts formed in rat mammary glands. / Todorovic, Rosa; Ariese, Freek; Devanesan, Prabhakar; Jankowiak, Ryszard; Small, Gerald J.; Rogan, Eleanor G; Cavalieri, Ercole.

In: Chemical Research in Toxicology, Vol. 10, No. 9, 01.09.1997, p. 941-947.

Research output: Contribution to journalArticle

Todorovic, Rosa ; Ariese, Freek ; Devanesan, Prabhakar ; Jankowiak, Ryszard ; Small, Gerald J. ; Rogan, Eleanor G ; Cavalieri, Ercole. / Determination of benzo[a]pyrene- and 7,12-dimethylbenz[a]anthracene-DNA adducts formed in rat mammary glands. In: Chemical Research in Toxicology. 1997 ; Vol. 10, No. 9. pp. 941-947.
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abstract = "Both 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (BP) are carcinogenic in the rat mammary gland. The depurinating and stable adducts of DMBA and BP formed in vitro and in mouse skin were previously identified and quantitated. Identification and quantitation of the depurinating and stable DNA adducts of DMBA and identification of the depurinating adducts of BP formed in rat mammary glands in the 24 h after intramammillary injection of DMBA or BP are reported in this paper. The depurinating adducts of DMBA, which constitute 52{\%} of all adducts detected, are DMBA bound at the 12- methyl group to the N-7 of adenine (Ade) or guanine (Gua), namely, 7- methylbenz[a]anthracene (MBA)-12-CH2-N7Ade (39{\%}) and 7-MBA-12-CH2-N7Gua (13{\%}). All of the stable adducts were formed from the diol epoxide(s) of DMBA. Depurinating adducts of BP with guanine, namely, 8-(BP-6-yl)-guanine (BP-6-C8Gua) and BP-6-N7Gua, were identified in rat mammary glands treated with BP. The major stable adduct, formed via the diol epoxide pathway, BP- diol epoxide-10-N2dG, accounted for over 64{\%} of all the stable adducts. Three other BP-DNA stable adducts remain unidentified. Thus, rat mammary cells form depurinating adducts of DMBA and BP predominantly via their radical cations and stable adducts via the diol epoxides.",
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T1 - Determination of benzo[a]pyrene- and 7,12-dimethylbenz[a]anthracene-DNA adducts formed in rat mammary glands

AU - Todorovic, Rosa

AU - Ariese, Freek

AU - Devanesan, Prabhakar

AU - Jankowiak, Ryszard

AU - Small, Gerald J.

AU - Rogan, Eleanor G

AU - Cavalieri, Ercole

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N2 - Both 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (BP) are carcinogenic in the rat mammary gland. The depurinating and stable adducts of DMBA and BP formed in vitro and in mouse skin were previously identified and quantitated. Identification and quantitation of the depurinating and stable DNA adducts of DMBA and identification of the depurinating adducts of BP formed in rat mammary glands in the 24 h after intramammillary injection of DMBA or BP are reported in this paper. The depurinating adducts of DMBA, which constitute 52% of all adducts detected, are DMBA bound at the 12- methyl group to the N-7 of adenine (Ade) or guanine (Gua), namely, 7- methylbenz[a]anthracene (MBA)-12-CH2-N7Ade (39%) and 7-MBA-12-CH2-N7Gua (13%). All of the stable adducts were formed from the diol epoxide(s) of DMBA. Depurinating adducts of BP with guanine, namely, 8-(BP-6-yl)-guanine (BP-6-C8Gua) and BP-6-N7Gua, were identified in rat mammary glands treated with BP. The major stable adduct, formed via the diol epoxide pathway, BP- diol epoxide-10-N2dG, accounted for over 64% of all the stable adducts. Three other BP-DNA stable adducts remain unidentified. Thus, rat mammary cells form depurinating adducts of DMBA and BP predominantly via their radical cations and stable adducts via the diol epoxides.

AB - Both 7,12-dimethylbenz[a]anthracene (DMBA) and benzo[a]pyrene (BP) are carcinogenic in the rat mammary gland. The depurinating and stable adducts of DMBA and BP formed in vitro and in mouse skin were previously identified and quantitated. Identification and quantitation of the depurinating and stable DNA adducts of DMBA and identification of the depurinating adducts of BP formed in rat mammary glands in the 24 h after intramammillary injection of DMBA or BP are reported in this paper. The depurinating adducts of DMBA, which constitute 52% of all adducts detected, are DMBA bound at the 12- methyl group to the N-7 of adenine (Ade) or guanine (Gua), namely, 7- methylbenz[a]anthracene (MBA)-12-CH2-N7Ade (39%) and 7-MBA-12-CH2-N7Gua (13%). All of the stable adducts were formed from the diol epoxide(s) of DMBA. Depurinating adducts of BP with guanine, namely, 8-(BP-6-yl)-guanine (BP-6-C8Gua) and BP-6-N7Gua, were identified in rat mammary glands treated with BP. The major stable adduct, formed via the diol epoxide pathway, BP- diol epoxide-10-N2dG, accounted for over 64% of all the stable adducts. Three other BP-DNA stable adducts remain unidentified. Thus, rat mammary cells form depurinating adducts of DMBA and BP predominantly via their radical cations and stable adducts via the diol epoxides.

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