Repair activity of base and nucleotide excision repair enzymes for guanine lesions induced by nitrosative stress

Nitric oxide (NO) induces deamination of guanine, yielding xanthine and oxanine (Oxa). Furthermore, Oxa reacts with polyamines and DNA binding proteins to form cross-link adducts. Thus, it is of interest how these lesions are processed by DNA repair enzymes in view of the genotoxic mechanism of NO. In the present study, we have examined the repair capacity for Oxa and Oxa–spermine cross-link adducts (Oxa–Sp) of enzymes involved in base excision repair (BER) and nucleotide excision repair (NER) to delineate the repair mechanism of nitrosative damage to guanine. Oligonucleotide substrates containing Oxa and Oxa–Sp were incubated with purified BER and NER enzymes or cell-free extracts (CFEs), and the damage-excising or DNA-incising activity was compared with that for control (physiological) substrates. The Oxa-excising activities of Escherichia coli and human DNA glycosylases and HeLa CFEs were 0.2–9% relative to control substrates, implying poor processing of Oxa by BER. In contrast, DNA containing Oxa–Sp was incised efficiently by UvrABC nuclease and SOS-induced E.coli CFEs, suggesting a role of NER in ameliorating genotoxic effects associated with nitrosative stress. Analyses of the activity of CFEs from NER-proficient and NER-deficient human cells on Oxa–Sp DNA confirmed further the involvement of NER in the repair of nitrosative DNA damage

Radon inhalation decreases DNA damage induced by oxidative stress in mouse organs via the activation of antioxidative functions

Radon inhalation decreases the level of lipid peroxide (LPO); this is attributed to the activation of antioxidative functions. This activation contributes to the beneficial effects of radon therapy, but there are no studies on the risks of radon therapy, such as DNA damage. We evaluated the effect of radon inhalation on DNA damage caused by oxidative stress and explored the underlying mechanisms. Mice were exposed to radon inhalation at concentrations of 2 or 20 kBq/m(3) (for one, three, or 10 days). The 8-hydroxy-2 '-deoxyguanosine (8-OHdG) levels decreased in the brains of mice that inhaled 20 kBq/m(3) radon for three days and in the kidneys of mice that inhaled 2 or 20 kBq/m(3) radon for one, three or 10 days. The 8-OHdG levels in the small intestine decreased by approximately 20-40% (2 kBq/m(3) for three days or 20 kBq/m(3) for one, three or 10 days), but there were no significant differences in the 8-OHdG levels between mice that inhaled a sham treatment and those that inhaled radon. There was no significant change in the levels of 8-oxoguanine DNA glycosylase, which plays an important role in DNA repair. However, the level of Mn-superoxide dismutase (SOD) increased by 15-60% and 15-45% in the small intestine and kidney, respectively, following radon inhalation. These results suggest that Mn-SOD probably plays an important role in the inhibition of oxidative DNA damage

Effects of irradiation on bone invasion of breast cancer cells

Background: Periostin is overexpressed in metastases from bone cancer. Many studies have indicated that periostin plays an important role in bone metastasis. Radiotherapy improves local tumor control, but recent evidence suggests that irradiation of the target tumor can promote tumor invasion and metastasis.Objective: The purpose of the study was to examine the effects of irradiation with carbon ion or gamma ray on the expression of periostin in breast cancer cells and the cytokine levels of osteoblasts in bone tumor metastases.Materials and methods: Breast cancer cells (FM3A/R cells) were exposed to carbon ion or gamma ray and then cocultured with non-irradiated osteoblastic MC3T3-E1 cells. Periostin expression in breast cancer cells and the levels of cytokines influencing bone invasion in osteoblastic cells were measured.Results: Periostin expression increased after irradiation with carbon ion or gamma ray. Carbon ion-irradiated cells expressed less periostin than did gamma ray-irradiated cells. Carbon ion irradiation stimulated low levels of periostin synthesis than gamma ray irradiation. The cytokines influencing bone invasion levels rose in tandem with the increase in periostin level.Conclusions: Carbon ion irradiation may reduce the production of bone-destroying cytokines and vascularization factors by osteoblasts in the microenvironment of cancer invasion in bone. A combination of carbon ion irradiation and a periostin inhibitor would improve treatment of bone metastatic breast cancer

Clustered DNA Damage by Heavy Ion Beams Irradiation and the Postirradiating Repair Process

3-PS3B-1915th International Congress of Radiation Researc