Identification of a novel, N7-deoxyguanosine adduct as the major DNA adduct formed by a non-bay-region diol epoxide of benzo[a]pyrene with low mutagenic potential

M. C. MacLeod, F. E. Evans, J. Lay, P. Chiarelli, N. E. Geacintov, K. L. Powell, Nicholas Geacintov, E. Luna, R. G. Harvey

Research output: Contribution to journalArticle

Abstract

A metabolite of benzo[a]pyrene,9-r,10-t-dihydroxy-7,8-c-oxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE-III), that is not thought to be involved in carcinogenesis has nevertheless been shown to bind extensively to DNA in vitro. The adducts formed by this non-bay-region diol epoxide in Chinese hamster ovary cells are much less mutagenic than those formed by an isomeric diol epoxide that is carcinogenic. We have isolated and characterized three major adducts formed by in vitro reaction of BPDE-III with DNA. The major adduct, accounting for over half of the total is formed by reaction of BPDE- III with the N7 position of dGuo and is recovered after enzymatic digestion as an N7-Gua adduct. A second major adduct involves the N2 position of dGuo, while the third adduct is tentatively identified as a C8-substituted dGuo. Little or no reaction with deoxyadenosine residues is detected. The N7 adduct is unstable in DNA at 37 °C and is released as the modified base with a half-life of about 24 h. This adduct lability apparently leads to single- strand breaks and alkali-sensitive sites in the DNA and may account in part for some of the biological properties of BPDE-III adducts. This represents the first description of an N7-dGuo adduct that is formed in DNA as the major adduct by a diol epoxide derived from a carcinogenic polycyclic aromatic hydrocarbon.

Original languageEnglish (US)
Pages (from-to)2977-2987
Number of pages11
JournalBiochemistry
Volume33
Issue number10
StatePublished - 1994

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Deoxyguanosine
DNA Adducts
Benzo(a)pyrene
Epoxy Compounds
DNA
Polycyclic Aromatic Hydrocarbons
Alkalies
Metabolites
Cricetulus
Half-Life
Digestion
Ovary
Carcinogenesis
Cells
BPDE-III

ASJC Scopus subject areas

  • Biochemistry
  • Medicine(all)

Cite this

MacLeod, M. C., Evans, F. E., Lay, J., Chiarelli, P., Geacintov, N. E., Powell, K. L., ... Harvey, R. G. (1994). Identification of a novel, N7-deoxyguanosine adduct as the major DNA adduct formed by a non-bay-region diol epoxide of benzo[a]pyrene with low mutagenic potential. Biochemistry, 33(10), 2977-2987.

Identification of a novel, N7-deoxyguanosine adduct as the major DNA adduct formed by a non-bay-region diol epoxide of benzo[a]pyrene with low mutagenic potential. / MacLeod, M. C.; Evans, F. E.; Lay, J.; Chiarelli, P.; Geacintov, N. E.; Powell, K. L.; Geacintov, Nicholas; Luna, E.; Harvey, R. G.

In: Biochemistry, Vol. 33, No. 10, 1994, p. 2977-2987.

Research output: Contribution to journalArticle

MacLeod, MC, Evans, FE, Lay, J, Chiarelli, P, Geacintov, NE, Powell, KL, Geacintov, N, Luna, E & Harvey, RG 1994, 'Identification of a novel, N7-deoxyguanosine adduct as the major DNA adduct formed by a non-bay-region diol epoxide of benzo[a]pyrene with low mutagenic potential', Biochemistry, vol. 33, no. 10, pp. 2977-2987.
MacLeod, M. C. ; Evans, F. E. ; Lay, J. ; Chiarelli, P. ; Geacintov, N. E. ; Powell, K. L. ; Geacintov, Nicholas ; Luna, E. ; Harvey, R. G. / Identification of a novel, N7-deoxyguanosine adduct as the major DNA adduct formed by a non-bay-region diol epoxide of benzo[a]pyrene with low mutagenic potential. In: Biochemistry. 1994 ; Vol. 33, No. 10. pp. 2977-2987.
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AU - MacLeod, M. C.

AU - Evans, F. E.

AU - Lay, J.

AU - Chiarelli, P.

AU - Geacintov, N. E.

AU - Powell, K. L.

AU - Geacintov, Nicholas

AU - Luna, E.

AU - Harvey, R. G.

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