Action of fludarabine on formation and removal of oxaliplatin ICL in specific genes of normal and CLL lymphocytes
. | Normal lymphocytes . | . | . | . | . | CLL lymphocytes . | . | . | . | . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | ICL/10 kb* . | . | Removal, %† . | . | Removal inhibition, %‡ . | ICL/10 kb* . | . | Removal, %† . | . | Removal inhibition, %‡ . | ||||||||
| Repair time, h . | Without fludarabine . | With fludarabine . | Without fludarabine . | With fludarabine . | . | Without fludarabine . | With fludarabine . | Without fludarabine . | With fludarabine . | . | ||||||||
| DHFR | ||||||||||||||||||
| 0 | 0.48 | 0.77 | — | — | — | 0.52 | 0.85 | — | — | — | ||||||||
| 4 | 0.29 | 0.53 | 40 | 31§ | 23 | 0.26 | 0.59 | 49 | 31§ | 37 | ||||||||
| 8 | 0.15 | 0.41 | 68 | 48§ | 29 | 0.08 | 0.42 | 85 | 51§ | 40 | ||||||||
| δ-Globin | ||||||||||||||||||
| 0 | 0.36 | 0.47 | — | — | — | 0.38 | 0.53 | — | — | — | ||||||||
| 4 | 0.26 | 0.36 | 29 | 23∥ | 21 | 0.19 | 0.33 | 51 | 38§ | 25 | ||||||||
| 8 | 0.20 | 0.30 | 45 | 37∥ | 15 | 0.13 | 0.25 | 65 | 53∥ | 19 | ||||||||
| mtDNA | ||||||||||||||||||
| 0 | 0.51 | 0.76 | 0 | 0 | — | 0.47 | 0.74 | — | — | — | ||||||||
| 4 | 0.34 | 0.56 | 34 | 26§ | 24 | 0.23 | 0.53 | 52 | 28§ | 46 | ||||||||
| 8 | 0.25 | 0.49 | 51 | 35§ | 25 | 0.12 | 0.37 | 75 | 50§ | 33 | ||||||||
. | Normal lymphocytes . | . | . | . | . | CLL lymphocytes . | . | . | . | . | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| . | ICL/10 kb* . | . | Removal, %† . | . | Removal inhibition, %‡ . | ICL/10 kb* . | . | Removal, %† . | . | Removal inhibition, %‡ . | ||||||||
| Repair time, h . | Without fludarabine . | With fludarabine . | Without fludarabine . | With fludarabine . | . | Without fludarabine . | With fludarabine . | Without fludarabine . | With fludarabine . | . | ||||||||
| DHFR | ||||||||||||||||||
| 0 | 0.48 | 0.77 | — | — | — | 0.52 | 0.85 | — | — | — | ||||||||
| 4 | 0.29 | 0.53 | 40 | 31§ | 23 | 0.26 | 0.59 | 49 | 31§ | 37 | ||||||||
| 8 | 0.15 | 0.41 | 68 | 48§ | 29 | 0.08 | 0.42 | 85 | 51§ | 40 | ||||||||
| δ-Globin | ||||||||||||||||||
| 0 | 0.36 | 0.47 | — | — | — | 0.38 | 0.53 | — | — | — | ||||||||
| 4 | 0.26 | 0.36 | 29 | 23∥ | 21 | 0.19 | 0.33 | 51 | 38§ | 25 | ||||||||
| 8 | 0.20 | 0.30 | 45 | 37∥ | 15 | 0.13 | 0.25 | 65 | 53∥ | 19 | ||||||||
| mtDNA | ||||||||||||||||||
| 0 | 0.51 | 0.76 | 0 | 0 | — | 0.47 | 0.74 | — | — | — | ||||||||
| 4 | 0.34 | 0.56 | 34 | 26§ | 24 | 0.23 | 0.53 | 52 | 28§ | 46 | ||||||||
| 8 | 0.25 | 0.49 | 51 | 35§ | 25 | 0.12 | 0.37 | 75 | 50§ | 33 | ||||||||
—indicates not applicable.
Values represent ICL/10 kb. Data are from at least 3 blots each of 3 independent biologic experiments. Standard errors for each group were in the range of 0 to 0.08 ICL/fragment.
Values represent percentage of ICL removal.
Values represent percentage of inhibition of ICL removal at 4 and 8 hours, determined as 1 = 1 - (percentage of ICL removal + fludarabine) / (percentage of ICL removal - fludarabine).
P < .05
P = .07.