Smoking related carcinogen-DNA adducts in biopsy samples of human urinary bladder: Identification of N-(deoxyguanosin-8-yl)-4-aminobiphenyl as a major adduct

Journal Article · Sat Jun 15 04:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.12.5350· OSTI ID:6100129

Talaska, G ^[1]; Al-Juburi, A Z.S.S. ^[2]; Kadlubar, F F ^[3]

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1. National Center for Toxicological Research, Jefferson, AR (United States) Univ. of Cincinnati, OH (United States)
2. John A. McClellan Memorial Veterans Administration Hospital, Little Rock, AR (United States)
3. National Center for Toxicological Research, Jefferson, AR (United States)

The prevalence of covalent modifications to DNA (carcinogen-DNA adducts) in 42 human urinary bladder biopsy samples was investigated by {sup 32}P-postlabeling methods, with enhancement by both nuclease P1 treatment and 1-butanol extraction. Total mean carcinogen-DNA adduct levels and the mean levels of several specific adducts were significantly elevated in DNA samples of 13 current smokers, as opposed to 9 never smokers or 20 ex-smokers (5 years abstinence). There was no significant difference between the latter two groups. Several DNA adducts enhanced by nuclease P1 treatment were chromatographically similar to putative hydrocarbon DNA adducts reported earlier for placenta and lung DNA samples obtained from cigarette smokers. Putative aromatic amine adducts were detected by 1-butanol extraction that were not present when the samples were treated with nuclease P1. One of these displayed chromatographic behavior identical to the predominant adduct induced by the human urinary bladder carcinogen, 4-aminobiphenyl, which is present in cigarette smoke. This adduct comigrated in several thin-layer chromatographic systems with a synthetic N-(deoxyguanosin-8-yl)-4-amino(2,2{prime}-{sup 3}H)biphenyl-3{prime},5{prime}-bisphosphate marker. These data reinforce an association between cigarette smoking and DNA damage and suggest a molecular basis for the initiation of human urinary bladder cancer by cigarette smoke.

• OSTI ID: 6100129
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:12; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
560300 -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
AEROSOLS
AMINES
ANIMALS
AROMATICS
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOPSY
BIPHENYL
BLADDER
BODY
CARCINOGENS
COLLOIDS
DAYS LIVING RADIOISOTOPES
DIAGNOSTIC TECHNIQUES
DISEASES
DISPERSIONS
DNA
DNA ADDUCTS
EPIDEMIOLOGY
FETAL MEMBRANES
HYDROCARBONS
ISOTOPES
LIGHT NUCLEI
LUNGS
MAMMALS
MAN
MEMBRANES
NEOPLASMS
NUCLEI
NUCLEIC ACIDS
ODD-ODD NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHOSPHORUS 32
PHOSPHORUS ISOTOPES
PLACENTA
POLYCYCLIC AROMATIC AMINES
POLYCYCLIC AROMATIC HYDROCARBONS
PRIMATES
RADIOISOTOPES
RESIDUES
RESPIRATORY SYSTEM
SMOKES
SOLS
TOBACCO SMOKES
URINARY TRACT
VERTEBRATES