Table 4.
Overview of adductome studies on NA crosslinks and simultaneous measurement of multiple species using LC-MS.
| Type | Sample source | MS type a | Scan mode b |
Fragmentation method |
Features of untargeted detection |
Adducts identified | Year | Reference |
|---|---|---|---|---|---|---|---|---|
| Crosslinks (DDCL) | Oligodeoxyribonucl eotides (ODNs) | Ion trap | DDA-MS2 | Trap-type CID | Specific mass increment on precursor ion due to cisplatin adduction | Cisplatin-derived intrastrand DDCL | 2013 | [202] |
| Crosslinks (DDCL) | CT-DNA | Q-LIT-Orbitrap | DDA-CNL-MS3 | MS2: trap-type CID MS3: HCD |
NL of dR, NL of 2 dR, NL of nB (Gua, Ade, Cyt, Thy), NL of 2 nB | Formaldehyde- and chlorambucil-derived DDCL | 2019 | [73] |
| Crosslinks (RPCL/DPCL) | CCRF-CEM T and GM639 cells | Q-LIT-Orbitrap | DDA-MS2 | Trap-type CID, HCD | Cys carbamidomethylati on, Met oxidation, N-terminal acetylation | Chemotherapy drug- or formaldehyde-induced crosslinks | 2020 | [203] |
| Crosslinks (DDCL) | CT-DNA | LIT-Orbitrap | DDA-CNL-MS3 | MS2: trap-type CID MS3: trap-type CID |
NL of dR, NL of 2 dR | Acrolein- and 4-hydroxy-2-nonenal-derived DDCL | 2010 | [204] |
| Crosslinks (DDCL) | CT-DNA, HT-29 cells | LIT-Orbitrap | DDA-CNL-MS3 | MS2: trap-type CID MS3: HCD |
NL of dR, NL of nB (Gua, Ade, Cyt, Thy) | Alkylating drug-derived DNA adducts and interstrand DDCL | 2015 | [66] |
| Crosslinks (DDCL) | CT-DNA, HT-29 and HCEC cells | Q-LIT-Orbitrap | DDA-CNL-MS3 | MS2: trap-type CID MS3: HCD |
NL of dR, NL of nB (Gua, Ade, Cyt, Thy) | Drug (PR104A)-derived DNA adducts and DDCL | 2017 | [205] |
| Crosslinks (DDCL) | CT-DNA, bacterium (E. coli), mice lung tissue, blood from dog with chemotherapy | Q-LIT-Orbitrap | DDA-CNL-MS3 | MS2: wide-HCD MS3: HCD |
NL of dR, NL of nB (Gua, Ade, Cyt, Thy) | Doxorubicin- and formaldehyde-derived DNA adducts and DDCL | 2021 | [206] |
| Crosslinks (DDCL) | 2'-dN, CT-DNA, oral rinse samples | Q-LIT-Orbitrap | DDA-CNL-MS3 | MS2: trap-type CID MS3: HCD |
NL of dR, NL of nB (Gua, Ade, Cyt, Thy) | Alcohol-derived DNA adducts and DDCL | 2021 | [207] |
| Crosslinks (DDCL) | CT-DNA | Q-LIT-Orbitrap | DDA-CNL-MS3 | MS2: trap-type CID MS3: wide-HCD |
NL of dR | Formaldehyde-derived DNA adducts and DDCL | 2021 | [56] |
| Crosslinks (DDCL) | CT-DNA, bacterium (E. coli), xenograft tumor tissue from NCr nude mice | Q-LIT-Orbitrap | DDA-CNL-MS3 | MS2: wide-HCD MS3: wide-HCD |
NL of dR, NL of nB (Gua, Ade, Cyt, Thy) | Drug (CP-506)-derived DNA adducts and DDCL | 2022 | [208] |
| Crosslinks (DDCL/DR CL) | 2'-dN, rN, mice lung tissue | Q-LIT-Orbitrap | DDA-CNL-MS3 | MS2: trap-type CID MS3: trap-type CID |
NL of dR, NL of nB (Gua, Ade, Cyt, Thy) | Formaldehyde-derived DDCL and DRCL | 2022 | [201] |
| Crosslinks (DDCL) | CT-DNA, bacterium (E. coli), whole blood | Q-LIT-Orbitrap | DDA-CNL-MS3 | MS2: HCD MS3: HCD |
NL of dR, NL of nB (Gua, Ade, Cyt, Thy), diagnostic product ion of fapy-specific fragments | Cyclophosphamide-derived DNA adducts and interstrand DDCL | 2023 | [180] |
| Crosslinks (RPCL) | U1 snRNP, snRNA | QTRAP | Precursor ion scan | Beam-type CID | Phosphate moiety (PO3−) | RPCL resulting from UV radiation | 2007 | [209] |
| Multi-species (DNA/RNA) | Garden cress (Lepidium sativum cv. Ogrodowa) | Ion trap | DDA-MS2 | Trap-type CID | NL of dR, NL of R | Methylated DNA and RNA adducts derived from cupric oxide nanoparticles | 2016 | [210] |
| Multi-species (DNA/RNA) | Hep G2 cells | QqQ | Pseudo-CNL | Beam-type CID | NL of dR, NL of R | B[a]P-derived DNA and RNA adducts | 2019 | [24] |
| Multi-species (DNA/protein) | ODNs, CT-DNA, human colorectal tumor tissue | Q-TOF | MSE | Beam-type CID | Cys methylation, Cys carbamidomethylation, Met oxidation, asparagine deamidation | O6-Alkylguanine species and alkylated cysteine | 2023 | [211] |
| Multi-species (DNA/RNA) | Baltic amphipod (Monoporeia affinis) | Q-Orbitrap | DIA | HCD | NL of dR, NL of R | DNA and RNA modifications | 2023 | [60] |
| Multi-species (DNA/RNA) and crosslinks) | 2'-dN, rN, amino acids, human urine | Q-LIT-Orbitrap | DDA-MS2 | Trap-type CID | NL of dR, NL of R, NL of MeR, NL of 2 dR, NL of 2 R, NL of 2 MeR, NL of R + MeR, NL of dR + R, NL of dR + MeR, NL of dR + Cys, NL of R + Cys, NL of MeR + Cys, diagnostic product ion of nB | DNA and RNA modifications, and a variety of crosslinks (DDCL/RRCL/DRC L/DPCL/RPCL) | 2023 | [38] |
| Multi-species (DNA/RNA) and crosslinks) | CT-DNA, yeast RNA, BSA, human urine | Q-LIT-Orbitrap | DDA-MS2 | Trap-type CID/wide-HCD | 132 features of NA modifications | DNA and RNA modifications, and a variety of crosslinks (DDCL/RRCL/DRC L/DPCL/RPCL) | 2024 | [58] |
a
LRMS includes QqQ, ion trap and QTRAP instruments while HRMS includes LIT-Orbitrap, Q-Orbitrap, Q-LIT-orbitrap, Q-TOF and TOF/TOF instruments.
b
Beam-type CID and HCD collisions in quadrupole or multipole cells typically produce numerous fragments, whereas trap-type CID collisions in ion traps yield fewer fragments.