TABLE 1.
Comparative toxicity and inhibition of protein translation in cytoplasmic and mitochondrial systems of G418, gentamicin, and the designer structures NB84 and NB74
| AG | Ototoxicity |
Cell toxicity (LC50) |
Translation inhibitiond |
||||
|---|---|---|---|---|---|---|---|
| Cochleotoxicity (LC50Coch)a | In vivob | HEK-293c | HeLa | In vitro IC50Cyto | Ex vivo IC50Mito | In vitro IC50Mito | |
| μm | mm | mm | μm | mm | μm | ||
| G418 | 0.7 | ++++ | 1.3 ± 0.1 | 2.1 ± 0.1 | 2.0 ± 0.3 | 2.3 ± 0.2 | 13 ± 1 |
| Gentamicin | 3.5 | ++ | 2.5 ± 0.3 | 2.9 ± 0. 2 | 62.0 ± 9.0 | 13.3 ± 0.4 | 26 ± 2 |
| NB84 | 20.0 | NDe | 5.8 ± 0.7 | 8.1 ± 1.3 | 2.8 ± 0.3 | >16 | 404 ± 26 |
| NB74 | 140.0 | + | 22.2 ± 1.1 | 27.4 ± 1.5 | 17.0 ± 0.6 | >16 | 965 ± 155 |
a LC50 values in human embryonic kidney (HEK-293) cells were previously reported (17).
b The cytoplasmic in vitro translation inhibition (IC50Cyto) and the mitochondrial in vitro translation inhibition (IC50Mito) were previously reported (17). The mitochondrial translation inhibition (IC50Mit) values ex vivo are derived from the data in Fig. 2B.
c Cochleotoxicity curves are presented in Fig. 7B.
d The relative ototoxicity in vivo are derived from the data in Fig. 7C.
e ND, not determined.