Fluorescence measurements of DNA-bound metabolites of benzo(a)pyrene derivatives with different carcinogenic effects.

Abstract:

:(+/-)-trans-dihydroxy-7,8-dihydrobenzo(a)pyrene (BP-7,8-diol) and 9-hydroxybenzo(a)pyrene (9-OH-BP) were metabolized by rat liver microsomes in the presence of calf thymus DNA, resulting in preferential DNA binding of fluorescent (+)-anti-BP-7,8-diol-9,10-epoxide (BPDE) and 9-OH-BP-4,5-epoxide, respectively. When the DNA is denatured the fluorescence intensities of the bound metabolites change in a characteristic manner. Fluorescence decay measurements show that the intensity changes are due to changes in lifetimes of the excited states. Model substances for the bound metabolites were studied in solvents of different polarity. We found that the fluorescence changes observed after denaturation of the DNA may be explained as solvent polarity effects, so that denaturation forces the bound metabolites from a more hydrophobic environment to a hydrophilic one. Fluorescence depolarization studies as a function of temperature in combination with previous linear dichroism studies show that both BPDE and 9-OH-BP-4,5-epoxide form rigidly associated complexes with native DNA.

journal_name

Toxicol Pathol

journal_title

Toxicologic pathology

authors

Gräslund A,Jernström B,Undeman O,Dock L,Ehrenberg A,Astlind T

doi

10.1177/019262338401200211

subject

Has Abstract

pub_date

1984-01-01 00:00:00

pages

179-84

issue

2

eissn

0192-6233

issn

1533-1601

journal_volume

12

pub_type

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