TY - JOUR
T1 - Kinetics of hydrolysis to tetraols and binding of benzo(a)pyrene-7,8-dihydrodiol-9,10-oxide and its tetraol derivatives to DNA. Conformation of adducts
AU - Geacintov, Nicholas E.
AU - Ibanez, Victor
AU - Gagliano, Antoine G.
AU - Yoshida, Hiroko
AU - Harvey, Ronald G.
N1 - Funding Information:
This investigation was supported by Grant awarded by the National Cancer Institute, Department Education and Welfare, and in part by Contracts from partment of Energy (EP-78-#-02-4959 and E(ll-1)2386) York University, and by American Cancer Society at the University of Chicago.
PY - 1980/2/27
Y1 - 1980/2/27
N2 - When the major reactive metabolite of benzo(a)pyrene, trans -7,8-dihydroxy - anti-9,10-epoxy -7,8,9,10-tetrahydrobenzo(a)pyrene (anti-BPDE) is incubated with DNA in aqueous solution at 25°C, both covalent binding and hydrolysis of anti-BPDE to its tetraols occur. Using fluorescence and absorption spectroscopy it is shown that hydrolysis of anti-BPDE is markedly accelerated by DNA. In the presence of 5A260 units of DNA per ml in cacodylate buffer solution, at an initial concentration of DNA phosphate/anti-BPDE ratio of 100, both the extent of covalent binding to DNA ( < 7% of the total anti-BPDE initially present) and hydrolysis of anti-BPDE reach their maximum levels within less than five minutes after mixing. Absorption and electric linear dichroism spectra indicate that the tetraols bind non-covalently to DNA by an intercalation mechanism, whereas the covalent product displays the characteristics of an externally bound complex.
AB - When the major reactive metabolite of benzo(a)pyrene, trans -7,8-dihydroxy - anti-9,10-epoxy -7,8,9,10-tetrahydrobenzo(a)pyrene (anti-BPDE) is incubated with DNA in aqueous solution at 25°C, both covalent binding and hydrolysis of anti-BPDE to its tetraols occur. Using fluorescence and absorption spectroscopy it is shown that hydrolysis of anti-BPDE is markedly accelerated by DNA. In the presence of 5A260 units of DNA per ml in cacodylate buffer solution, at an initial concentration of DNA phosphate/anti-BPDE ratio of 100, both the extent of covalent binding to DNA ( < 7% of the total anti-BPDE initially present) and hydrolysis of anti-BPDE reach their maximum levels within less than five minutes after mixing. Absorption and electric linear dichroism spectra indicate that the tetraols bind non-covalently to DNA by an intercalation mechanism, whereas the covalent product displays the characteristics of an externally bound complex.
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U2 - 10.1016/0006-291X(80)90432-5
DO - 10.1016/0006-291X(80)90432-5
M3 - Article
C2 - 6768360
AN - SCOPUS:0018830201
VL - 92
SP - 1335
EP - 1342
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -