Dosimetry of PAH skin carcinogenesis: covalent binding of benzo(a)pyrene to mouse epidermal DNA

Journal Article · Sat Jan 01 00:00:00 EST 1983 · Carcinogenesis (N.Y.); (United States)

DOI:https://doi.org/10.1093/carcin/4.2.195· OSTI ID:6267656

Shugart, L; Holland, J M; Rahn, R O

Benzo(a)pyrene (BaP) is metabolized to the chemically reactive anti and syn isomers of the 7,8-diol-9,10-epoxides of BaP (BPDE) which bind covalently to DNA to form DNA/BPDE complexes. Tetrols liberated from the DNA/BPDE complex by acid hydrolysis are easily quantified by h.p.l.c. using fluorescence detection. This approach allows femtomole amounts of BPDE associated with the DNA isolated from a single mouse to be detected using conventional instrumentation. The usefulness of this technique to estimate the interaction of BaP with DNA of mouse skin, both in the intact animal and in organ culture, was investigated. With mouse skin in organ culture it could be demonstrated that: (1) upon a single topical application of 5 ..mu..g of BaP, binding to DNA occurred via BPDE at a linear rate for up to 65 h, (2) the amount of binding was dose dependent at concentrations of BaP <10 ..mu..g.

• Research Organization: Oak Ridge National Lab., TN
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 6267656
• Journal Information: Carcinogenesis (N.Y.); (United States), Vol. 4:2
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BENZOPYRENE
DOSE-RESPONSE RELATIONSHIPS
METABOLIC ACTIVATION
CHEMICAL BONDS
DNA
EPIDERMIS
LIQUID COLUMN CHROMATOGRAPHY
METABOLITES
MICE
NUMERICAL DATA
STEREOCHEMISTRY
TISSUE CULTURES
ANIMAL TISSUES
ANIMALS
AROMATICS
BODY
CHROMATOGRAPHY
CONDENSED AROMATICS
DATA
EPITHELIUM
HYDROCARBONS
INFORMATION
MAMMALS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANS
RODENTS
SEPARATION PROCESSES
SKIN
TISSUES
VERTEBRATES
560305* - Chemicals Metabolism &amp; Toxicology- Vertebrates- (-1987)