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Inhibition of DNA repair and the enhancement of cytotoxicity of alkylating agents by Oskar S. Frankfurt is a Medicine article available to read on EtoBox.

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## Abstract DNA damage was evaluated by flow cytometric (FCM) analysis of cells treated with L‐phenylalanine mustard (L‐PAM) and stained with anti‐DNA monoclonal antibody (MAb) F7–26. DNA damage was rapidly repaired, as indicated by the loss of DNA immunoreactivity after removal of L‐PAM. Two types of drug combinations were found to inhibit DNA repair. Combinations containing inhibitors of DNA polymerase (ara‐C, aphidicolin) or these inhibitors and hydroxyurea inhibited DNA repair in A2780/PAM and A549 cells. The inhibition of DNA repair by combinations of DNA‐damaging agents thloTEPA or cisplatln and DNA polymerase inhibitors is a novel observation based on the specificity of DNA damage assay with MAb F7–26. Combinations containing thioTEPA or cisplatin inhibited DNA repair in A549 but not in A2780/PAM cells. Drug combinations which inhibited DNA repair also significantly enhanced cell killing by L‐PAM. Cell survival in cultures treated with L‐PAM and efficient inhibitors was 2 to 3 orders of magnitude lower than was expected for additive survival. ThioTEPA and cisplatin play a dual role in combination chemotherapy by inducing DNA damage and inhibiting repair of DNA damage. FCM an

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Author

Oskar S. Frankfurt

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); John Wiley & Sons Inc.; Wiley; Research Square; Test accounts (ISSN 0020-7136)

Published

1991

Language

EN

Field

Medicine (Health Sciences)