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ON BENZO[A]PYRENE DERIVED DNA ADDUCTS FORMED IN LUNG TISSUE OF MICE
Citation:
Banasiewicz, M., G. Nelson, A E. Swank, N. Grubor, J. Small, J A. Ross, S. C. Nesnow, AND R. Jankowiak. ON BENZO[A]PYRENE DERIVED DNA ADDUCTS FORMED IN LUNG TISSUE OF MICE. Presented at Pittcon Conference, Chicago, IL, March 7-12, 2004.
Description:
On Benzo [a] pyrene Derived DNA Adducts Formed in Lung Tissue of Mice
The previously identified major DNA adducts of benzo[a]pyrene (BP) in vitro and in vivo are the stable and unstable adducts formed by reaction of the bay-region diol epoxide of BP (BPDE) and BP radical cation with DNA, respectively. Unstable adducts are lost from DNA by depurination. We will discuss the BPDE-DNA adduct conformations formed at low adduction level (about one DNA adduct per 107 bases) and the nature of depurinating adducts formed in DNA of lung tissue in five A/J strain mice exposed to BP by a single intraperitoneal injection. Identification and quantitation of stable BPDE-derived DNA adducts are achieved by low temperature fluorescence spectroscopy and 32P-postlabeling methodology, respectively. DNA extraction washes (supernatants) were used for the analysis of depurinating adducts, which were studied by a combination of HPLC and capillary electrophoresis with both absorbance and fluorescence detection. It is shown that (i) DNA extracted from the lung tissue of mice exposed to BP for two and three days contained 460-500 and 670-940 attomoles of BPDE-derived adducts/ug of DNA, respectively; (ii) the major BPDE-adducts exist in both external (trans-type BPDE-DNA adducts) and intercalated conformations (cis-type BPDE-DNA adducts); (iii) the trans-/cis-BPDE-adducts ratio is significantly lower than that observed in vitro at higher adduction levels; and (iv) the formation of depurinating BP-DNA adducts and the relative distribution of BPDE-DNA adduct conformations and adduct types varies for BP treated mice.
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