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Excisability and persistence of benzo(a)pyrene DNA adducts in epithelioid human lung cells

Nature volume 274, pages 796798 (24 August 1978) | Download Citation

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Abstract

RESIDUAL DNA lesions in the template strand during replication may represent the ‘stumbling blocks’ responsible for mutagenesis and initiation of malignant transformation. The fraction of specific lesions which remains unexcised at the time of DNA replication is determined by their ‘excisability’1 in a particular tissue. Lesions which become refractory to excision and remain in the DNA over many generations, referred to as ‘persistent lesions’, may play a crucial role in the transformation process2–4. We have studied the ‘excisability’ and ‘persistence’ of the covalent DNA adducts produced in the epithelioid human alveolar tumour cell A549 (ref. 5) by benzo(a)pyrene (B(a)P)6, and found that the excisability of the covalent B(a)P–DNA adducts in A549 cells was poor and that a sizeable fraction of the lesions persisted over several generations. The poor repairability by excision of these and related lesions in human lung cells may represent a factor in lung carcinogenesis by polycyclic aromatic hydrocarbons.

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Author information

Author notes

    • KUNIO SHINOHARA

    Present address: Department of Radiation Biophysics, School of Medicine, Kobe University, Kusunoki-cho 7-12-1, Ikuta-ku, Kobe-shi, Hyogo 659, Japan.

    • PETER CERUTTI

    Address for reprint requests: Department of Carcinogenesis, Swiss Institute for Experimental Cancer Research, 1066 Epalinges, Switzerland.

Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Florida, J. H. Miller Health Center, Gainesville, Florida 32610

    • GEORGE FELDMAN
    • , JOYCE REMSEN
    • , KUNIO SHINOHARA
    •  & PETER CERUTTI

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DOI

https://doi.org/10.1038/274796a0

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