TABLE 1.
Genotoxic agent effects on DNA structure, DNA repair, and transcription
| Genotoxic agent | DNA adduct | Bendinga (major groove)(°) | Repairb | Transcription inhibitionc | Transcription factor bindingc
|
Toxicityd | |
|---|---|---|---|---|---|---|---|
| TFIIH (p62) | TFIID (TBP) | ||||||
| CDDP | 1,2-d(GpG) | 32–58 | + (NER) | + | + | + | +++ |
| 1,3-d(GpXpG) | 20–35 | ++ (NER) | NDe | + | ± | ||
| TDDP | 1,3-d(GpXpG) | 26 | ++ (NER) | ± | + | ± | ± |
| Dach | 1,2-d(GpG) | ND | + (NER) | + | + | + | +++ |
| 1,3-d(GpXpG) | 20–35 | ++ (NER) | ND | + | ± | ||
| Dien | 1N7G | 0 | + (NER) | − | ± | − | − |
| AAF | 1C8G | ND | ++ (NER) | + | + | + | ND |
| MMS | 1N7G | ND | +++ (BER) | − | − | − | +++ |
| EtAz | ND | + (NER)/+ (BER) | ± | + | − | ND | |
| UVC | T-T | 30 | ++ (NER) | + | + | + | +++ |
a
Bending angle was calculated by nuclear magnetic resonance, X-ray diffraction, and gel shift assay (3, 27, 43).
b
+ to +++, lowest to highest level, respectively.
c
+, inhibition or binding; −, no inhibition or binding; ±, mixed result.
d
+++, highly cytotoxic; ±, weakly cytotoxic; −, no effect. The sensitivity of HeLa cells to the genotoxic agents used in this study was assessed by colony formation assay.
e
ND, not determined.