Figure 10: Mgst2 deficiency and LTC4 inhibition attenuate 5-FU-triggered DNA damage and toxicity.
From: Leukotriene C4 is the major trigger of stress-induced oxidative DNA damage

(a) Survival of WT and Mgst2-deficient mice (10 per group) given 5-FU (300 mg kg−1, ip) at time=0. P=0.0085. (b) Survival of WT 129/Sv mice (18 per group) treated with 5-FU as in a. Vehicle or pranlukast (1 mg kg−1) were administered at days 0, 1, 2, 5, 6 and 7. P=0.032. The statistical significance was determined in a and b using the Gehan–Breslow–Wilcoxon test. (c) Haematoxylin–eosin (H&E) stain and immunostain of the indicated proteins and 8-OHdG in kidney slices of WT mice treated with 5-FU (300 mg kg−1, ip at time=0) followed by five administrations of PBS or pranlukast (Pran., 3 mg kg−1, ip) as in b. Kidneys were processed at day 13. Bar, 50 μm. Insets: enlarged images showing immunostained nuclei. The images of kidney slices are representatives of slices from three mice per group. (d) Survival of U266 myeloma cells treated with bortezomib alone or together with the indicated LTC4 inhibitors (10 μM each). n=3. (e) Survival of CCRF-CEM T-cell leukaemia lymphoblasts treated with doxorubicin together with the indicated LTC4 inhibitors (10 μM each). n=3. No significant differences were found between vehicle and any of the inhibitors in d and e. Statistical significance was determined using one-way ANOVA.