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Time‐resolved fluorescence studies of the effects of metabolism on the In Vitro reversible binding and accumulation of benzo[a]pyrene in DNA
Author(s) -
Prakash A. S.,
Zegar I. S.,
Price H. L.,
Lebreton P. R.
Publication year - 2009
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560300823
Subject(s) - pyrene , chemistry , carcinogen , benzo(a)pyrene , metabolite , dna , polycyclic aromatic hydrocarbon , hydrocarbon , fluorescence , metabolism , stereochemistry , biochemistry , organic chemistry , physics , quantum mechanics
Time‐resolved fluorescence techniques have been employed to compare the DNA association constant of the parent hydrocarbon benzo[a]pyrene versus that of trans ‐7, 8‐dihydroxy‐7, 8‐dihydrobenzo[a]pyrene. The latter molecule is a highly carcinogenic metabolite derived from benzo[a]pyrene. Solubilization experiments were also carried out to compare the maximum total uptake of benzo[a]pyrene and of the metabolite by DNA. In the solvent system used in the association constant measurements (20% methanol) the association constant for benzo[a]pyrene is 3.0+0.3 × 10 4 M ‐1 while that of the more polar proximate carcinogen is 7.5 times lower. The results of the solubilization studies carried out in buffered aqueous medium demonstrate that at a DNA concentration of 5 × 10 ‐4 M in PO ‐ 4 the maximum uptake of benzo[a]pyrene into DNA is one molecule per 2.2+0.5 × 10 3 nucleotide bases. The maximum uptake of the more soluble proximate carcinogen is 4 to 25 times greater than that of the parent hydrocarbon. The present results indicate that metabolism of benzo[a]pyrene leads to the formation of a nonreactive proximate carcinogen which has a lower binding constant than the parent hydrocarbon, but which is better able to diffuse through a polar medium and to accumulate at ultimate biological target sites.