Kinetic study on the in vitro covalent binding of polycyclic hydrocarbons to nucleic acids using epidermal homogenates as the activating system
Journal Article
·
· Cancer Res.; (United States)
OSTI ID:6421972
Several variables were studied in relation to the covalent binding of radioactive polycyclic aromatic hydrocarbon (PAH) tumor initiators to nucleic acids by epidermal aryl hydrocarbon hydroxylase in vitro. Initially, the binding of 3-methylcholanthrene (MC) to DNA was linear, although a leveling off was observed with increased concentrations of substrate, enzyme, DNA, and reduced nicotinamide adenine dinucleotide phosphate (NADPH). Covalent binding of MC and benzo(a)pyrene (BP) to DNA in vitro by an NADPH-dependent epidermal homogenate was linear for 90 min, after which it leveled off. A second addition of NADPH resulted in a linear increase in DNA binding lasting approximately 90 min more. At 12 hr after induction at various times with the corresponding unlabeled PAH, the specific activities of MC, BP, 7,12-dimethylbenz(a)anthracene, dibenz(a,h)anthracene, and dibenz(a,c)anthracene binding to DNA by epidermal homogenates in vitro all peaked. A correlation exists between the tumor-initiating ability of several PAH's and their ability to bind covalently to DNA in vitro with the use of mouse epidermal homogenates and NADPH as an electrophile-generating system (7,12-dimethylbenz(a)anthracene > MC > BP > dibenz(a,h) anthracene > dibenz(a,c)anthracene). With the exception of DMBA, each of these PAH's possesses a strong need for NADPH. The specific activity of BP binding to various nucleic acids was: Polyguanylic acid > polyadenylic acid > yeast RNA > DNA.
- Research Organization:
- Oak Ridge National Lab., TN
- OSTI ID:
- 6421972
- Journal Information:
- Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 37; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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·
Tue Mar 04 23:00:00 EST 1986
· Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
·
OSTI ID:6962291
Related Subjects
550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
AROMATICS
BENZANTHRACENE
BINDING ENERGY
BIOCHEMICAL REACTION KINETICS
BODY
COENZYMES
CONDENSED AROMATICS
DNA
ENERGY
EPIDERMIS
EPITHELIUM
HOMOGENATES
HYDROCARBONS
KINETICS
NADP
NUCLEIC ACIDS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
POLYCYCLIC AROMATIC HYDROCARBONS
REACTION KINETICS
SKIN
TISSUES
59 BASIC BIOLOGICAL SCIENCES
AROMATICS
BENZANTHRACENE
BINDING ENERGY
BIOCHEMICAL REACTION KINETICS
BODY
COENZYMES
CONDENSED AROMATICS
DNA
ENERGY
EPIDERMIS
EPITHELIUM
HOMOGENATES
HYDROCARBONS
KINETICS
NADP
NUCLEIC ACIDS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANS
POLYCYCLIC AROMATIC HYDROCARBONS
REACTION KINETICS
SKIN
TISSUES