Binding of the carcinogens 5-fluoro-7-hydroxymethyl-12-methylbenz(a)anthracene and its acetate ester to DNA in vitro
Binding of 5-fluoro-7-hydroxymethyl-12-methylbenz(a)anthracene to calf thymus DNA was negligible (1.2 ..mu..mole hydrocarbon/mole DNA-P) in the absence of microsomal enzymes whereas in the presence of liver microsomes from unpretreated rats or from rats pretreated with 3-methylcholanthrene binding was greatly enhanced (11.6 and 16.2 ..mu..mole hydrocarbon/mole DNA-P respectively). In contrast, the acetate ester of 5-fluoro-7-hydroxymethyl-12-methylbenz(a)anthracene readily bound to DNA non-enzymatically (9.1 ..mu..mole hydrocarbon/mole DNA-P). In the presence of a 3'-phosphoadenosine-5'-phosphosulfate (PAPS) generating system, the binding of 5-fluoro-7-hydroxymethyl-12-methylbenz(a)anthracene was independent of sulfate ion. ATP enhanced non-enzymatic binding of 5-fluoro-7-hydroxymethyl-12-methylbenz(a)anthracene to DNA whereas CTP, ..beta..,..gamma..-methylene-ATP, and ADP were much less effective suggesting a certain specificity for adenosine in addition to a high energy triphosphate for high binding. These observations suggest that 5-fluoro-7-hydroxymethyl-12-methylbenz(a)anthracene may be converted to a phosphate ester which, like 5-fluoro-7-acetoxymethyl-12-methylbenz(a)anthracene, readily binds to DNA.
- Research Organization:
- Univ. of Kentucky, Lexington
- OSTI ID:
- 5705519
- Journal Information:
- Life Sci.; (United States), Vol. 28:10
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CARCINOGENS
CHEMICAL ACTIVATION
DIMETHYLBENZANTHRACENE
BIOCHEMISTRY
INTERACTIONS
DNA
CALVES
ESTERS
METABOLISM
METABOLITES
THYMUS
ANIMALS
AROMATICS
BODY
CATTLE
CHEMISTRY
CONDENSED AROMATICS
DOMESTIC ANIMALS
LYMPHATIC SYSTEM
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RUMINANTS
VERTEBRATES
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)