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. Author manuscript; available in PMC: 2022 Jun 21.
Published in final edited form as: DNA Repair (Amst). 2020 Jul 10;94:102926. doi: 10.1016/j.dnarep.2020.102926

Table 1.

Inducers of TOP-DPC including anticancer drugs, common DNA alterations and transactions, carcinogenic physical agents and metabolic products and DNA repair defects.

Inducers Molecular mechanism TOP1-DPC TOP2-DPC References
Anticancer drugs TOP1 and TOP2 poisons Interfacial inhibition with a single drug molecule bound at the DNA break-topoisomerase interface

  • Camptothecins: Topotecan, Irinotecan, Belotecan, Onivyde, Enhertu and other ADCs

  • Indenoisoquinolines: LMP400 (Indotecan), LMP776 (Indimitecan), LMP744)

  • Non-intercalators (Etoposide, Teniposide)

  • DNA intercalating agents: Amsacrine, Anthracyclines: Doxorubicin, Daunorubicin, Epirubicin, Idarubicin: Mitoxantrone

 [193,194,195,196]
Platinum salts DNA distortion Cisplatin, carboplatin Unknown [197]
Antimetabolites DNA distortions; ribonucleotide incorporations Hydroxyurea, Gemcitabine, Cytarabine, Fluorodeoxyruridine Unknown [19,20,160,198,199,200,201,202,203]
Others Distortion of DNA minor groove Hoechst 33342
Nogalamycin
Actinomycin D		 Actinomycin D [204,205,206,207,208,209]
Carcinogens Food & environmental products DNA distortions & topoisomerase alterations Trapping by carcinogenic base damage, exocyclic adducts, crosslinks, benzo[a] pyrene & crotonaldehyde adducts Trapping by flavone derivatives, tea and wine products & carcinogenic base adducts [5,203,210,211,212,213,214,215,216,217,218,219,220,221]
UV adducts & IR-induced DNA damage DNA distortions, base alterations & breaks Trapping by DNA alterations Trapping by DNA alterations and enzymatic inhibition [222,223,224] [16,17,18,218,225]
Endogenous metabolites & DNA alterations ROS - aldehydes DNA distortions DNA alterations DNA alterations [215,219,226,227]
Abasic sites, mismatches, DNA breaks DNA distortions DNA distortions DNA distortions [16,17,18,19,20,218,219,225,228,229,230]
Ribonucleotide incorporation in DNA Chemical reactivity & DNA distortions Trapping of flanking TOP1cc Trapping of TOP2cc [19,20,160,198,199,200]
Transcription Unknown Unknown Enhancers Promoters [35,36,37,38,39,40]
DNA repair defects Genetic alterations Lack of TOP-DPC excision TDP1, SPRTN, RNase H2 and ATM deficiencies TDP2 deficiency and MRE11 [23,25,27,35,129,231,232,233,234]