Noncovalent binding of 7. beta. ,8. cap alpha. -dihydroxy-9. cap alpha. ,10. cap alpha. -epoxytetrahydrobenzo(a)pyrene to deoxyribonucleic acid and its catalytic effect on the hydrolysis of the diol epoxide to tetrol

Journal Article · Tue Apr 13 00:00:00 EST 1982 · Biochemistry; (United States)

OSTI ID:5473500

Geacintov, N E ^[1]; Yoshida, H; Ibanez, V; Harvey, R G

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1. New York Univ., New York

In the presence of native DNA the hydrolysis of benzo(a)pyrene-7,8-diol 9,10-epoxide (BPDE) to tetrols (BPT) is markedly accelerated (by a factor of up to approx.80 at 25/sup 0/ C, pH 7.0, in 5 mM sodium cacodylate buffer solution). When stopped-flow kinetic techniques are utilized, it is shown that the pseudo-first-order hydrolysis rate constant k/sub H/ is smaller by a factor of approx.3 in the presence of equivalent concentrations of denatured DNA, by a factor of 8-25 in the presence of nucleotides, and by a factor of 35-45 in the presence of nucleosides (depending on the nucleotide or nucleoside). In the presence of native DNA, k/sub H/ increases with increasing DNA concentration and reaches a limiting value of k/sub H/ = 0.684 +/- 0.04 s/sup -1/ at DNA concentrations in excess of approx.5 X 10/sup -4/ M (expressed in concentration of nucleotides). A kinetic model based on (1) rapid formation of a noncovalent BPDE-DNA complex followed by (2) slower hydrolysis of BPDE to BPT at these binding sites is consistent with the experimental data. It is shown furthermore that the DNA is similar and that addition of magnesium ions (which is known to reduce intercalative binding of planar aromatic molecules to DNA) also reduces k/sub H/. These results suggest, but do not necessarily prove, that DNA binding sites at which the hydrolysis of BPDE (to BPT) is catalyzed are intercalative in nature.

• DOE Contract Number: AC02-78EV04959; E(11-11)2386
• OSTI ID: 5473500
• Journal Information: Biochemistry; (United States), Vol. 21:8
• Country of Publication: United States
• Language: English

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