Benzo(a)pyrene diol epoxide I binds to DNA at replication forks

Journal Article · Fri Apr 01 04:00:00 EST 1988 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.85.7.2176· OSTI ID:6832529

Paules, R S; Cordeiro-Stone, M; Kaufman, D G ^[1]; Mass, M J ^[2]; Poirier, M C; Yuspa, S H ^[3]

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1. Univ. of North Carolina, Chapel Hill (USA)
2. Environmental Protection Agency, Research Triangle Park, NC (USA)
3. National Cancer Institute, Bethesda, MD (USA)

The distribution of lesions in DNA caused by benzo(a)pyrene (B(a)P diol epoxide-I) was studied in synchronized C3H/10T1/2 cells treated in S phase. Sites of carcinogen modification of DNA were identified by polyclonal rabbit antibodies elicited against DNA modified with B(a)P diol epoxide-I in vitro. This antigenic DNA contained trans-(7R)-N{sup 2}-(10-(7{beta},8{alpha},9{alpha}-trihydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene)-yl)-deoxyguanosine; other adducts were not detected by liquid chromatography. In this study, DNA replication forks with antibodies bound to B(a)P diol epoxide-I adducts were detected by electron microscopy. The frequency of replication forks containing carcinogen adducts associated with the fork junction was found to be 8-fold higher than expected for an average distribution. The proportion of replication forks that were apparently blocked at the site of the DNA damage increased when replication was allowed to occur after carcinogen exposure. These results support the conclusions that the fork junction is particularly vulnerable to adduction by B(a)P diol epoxide-I and that B(a)P diol epoxide-I adducts block the displacement of replication forks during DNA synthesis in intact cells.

• OSTI ID: 6832529
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 85:7; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADDUCTS
ANIMAL CELLS
ANIMALS
ANTIBODIES
AROMATICS
BENZOPYRENE
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
CONDENSED AROMATICS
CONNECTIVE TISSUE CELLS
DNA
DNA ADDUCTS
DNA REPLICATION
ELECTRON MICROSCOPY
FIBROBLASTS
HYDROCARBONS
INHIBITION
KINETICS
MAMMALS
MICE
MICROSCOPY
MOLECULAR STRUCTURE
NUCLEIC ACID REPLICATION
NUCLEIC ACIDS
ORGANIC COMPOUNDS
RABBITS
REACTION KINETICS
RODENTS
SOMATIC CELLS
TIME DEPENDENCE
TRANSMISSION ELECTRON MICROSCOPY
VERTEBRATES