Time-resolved fluorescence studies of the effects of metabolism on the In Vitro reversible binding and accumulation of benzo[a]pyrene in DNA

Autor: I. S. Zegar, Pierre R. LeBreton, H. L. Price, Anand Prakash
Rok vydání: 2009
Předmět:
Zdroj: International Journal of Quantum Chemistry. 30:237-250
ISSN: 1097-461X
0020-7608
DOI: 10.1002/qua.560300823
Popis: 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 × 104M-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 × 10-4M in PO-4 the maximum uptake of benzo[a]pyrene into DNA is one molecule per 2.2+0.5 × 103 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.
Databáze: OpenAIRE
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