To elucidate the role of the mismatch repair gene Mlh1 in genome instability during the fetal stage, spontaneous mutations were studied in Mlh1 -deficient lacZ -transgenic mouse fetuses. Mutation levels were high at 9.5 days post coitum (dpc) and gradually increased during the embryonic stage, after which they remained unchanged. In addition, mutations that were found in brain, liver, spleen, small intestine and thymus showed similar levels and no statistically significant difference was found. The molecular nature of mutations at 12.5 dpc in fetuses of Mlh1 +/+ and Mlh1 –/– mice showed their own unique spectra, suggesting that deletion mutations were the main causes in the deficiency of the Mlh1 gene. Of note, fetuses of irradiated mice exhibited marked differences such as post-implantation loss and Mendelian distribution. Collectively, these results strongly suggest that high mutation of Mlh1 –/– -deficient fetuses has little effect on the fetuses during their early developmental stages, whereas Mlh1 –/– -deficient fetuses from X-ray irradiated mothers are clearly effected.
Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis . It is a traditional medicinal that is used for wound healing and to stop bleeding. Its main biological activity appears to be from phenolic compounds found in Dragon's blood. In this study, the radioprotective effects of Dragon's blood were examined after whole brain irradiation of rats with either 100 MeV/u Carbon 12 C 6+ heavy ions or 60 Co γ-rays. The amounts of radiation-induced oxidative stress, inflammatory cytokines and apoptosis in irradiated rat brains were compared with and without Dragon's blood treatment. Compared to the “irradiation only” control group, the Dragon's blood treatment group significantly decreased malondialdehyde and hydrogen peroxide levels, and increased superoxide dismutase activity and glutathione levels induced by oxidative stress in radiation exposed rats ( P < 0.05). Dragon's blood also significantly reduced radiation-induced inflammatory cytokines of tumor necrosis factor-α, interferon-γ and interleukin-6 levels ( P < 0.05) and inhibited hippocampal neuronal apoptosis in 60 Co γ-ray irradiated rats. Furthermore, Dragon's blood significantly increased expression of brain-derived neurophic factor and inhibited the expression of pro-apoptotic caspase 3 ( P < 0.05–0.01). Finally, Dragon's blood significantly inhibited expression of the AP-1 transcription factor family members c-fos and c-jun proteins ( P < 0.05–0.01). The results obtained here suggest that Dragon's blood has radioprotective properties in rat brains after both heavy ions and 60 Co γ-ray exposure.