Benzoyl peroxide (BzPO), a free-radical generator, has tumor-promoting activity. As a method for approaching the mechanism of tumor promoter function, the ability of oxidative DNA damage by BzPO was investigated by using (32)P-labeled DNA fragments obtained from the human p53 tumor suppressor gene and c-Ha-ras-1 protooncogene. BzPO induced piperidine-labile sites at the 5'-site guanine of GG and GGG sequences of double-stranded DNA in the presence of Cu(I), whereas the damage occurred at single guanine residues of single-stranded DNA. Both methional and dimethyl sulfoxide (DMSO) inhibited DNA damage induced by BzPO and Cu(I), but typical hydroxyl radical ((*)OH) scavengers, superoxide dismutase (SOD) and catalase, did not inhibit it. On the other hand, H(2)O(2) induced piperidine-labile sites at cytosine and thymine residues of double-stranded DNA in the presence of Cu(I). Phenylhydrazine, which is known to produce phenyl radicals, induced Cu(I)-dependent damage at thymine residues but not at guanine residues. These results suggest that the BzPO-derived reactive species causing DNA damage is different from (*)OH and phenyl radicals generated from benzoyloxyl radicals. BzPO/Cu(I) induced 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) formation in double-stranded DNA more effectively than that in single-stranded DNA. Furthermore, we observed that BzPO increased the amount of 8-oxodG in human cultured cells. Consequently, it is concluded that benzoyloxyl radicals generated by the reaction of BzPO with Cu(I) may oxidize the 5'-guanine of GG and GGG sequences in double-stranded DNA to lead to 8-oxodG formation and piperidine-labile guanine lesions, and the damage seems to be relevant to the tumor-promoting activity of BzPO.

Our results present the current clinical preferences of anti-VEGF treatment for DME in Japan. The best-corrected visual acuity and the retinal thickness are important indicators to institute this therapy. The majority of the ophthalmologists use anti-VEGF treatment as first-line therapy and prefer the 1 + pro re nata regimen.

PurposeTo study changes in the opening angle of the optic nerve and the angle of the ocular orbit with increasing age in normal Japanese children.MethodsWe studied 147 normal children (aged 6 months to 18 years) who had undergone CT as a diagnostic procedure. Measurements were performed on axial CT images that included the entire optic nerve of both eyes. The opening angle of the optic nerve was defined as the angle formed by the intersection of a line running through the left optic nerve and a vertical line passing through the centre of the nose. The opening angle of the orbit was defined as the angle formed by the intersection of a line running tangentially along the deep lateral wall of the left orbit and a vertical line passing through the centre of the nose. The relationship between age and these opening angles was analysed by regression analysis.ResultsThe correlation between age and opening angle of the optic nerve was not significant. In contrast, the opening angle of the orbit decreased relatively rapidly until about 2–3 years of age, and then it stabilised. The decrease in the opening angle of the orbit with increasing age was significant (p<0.001). The relationship between these two parameters was best fitted by a logarithmic regression curve.ConclusionsBecause the opening angle of the orbit decreased significantly with increasing age, this factor must be considered when diagnosing and treating strabismus in children.

By using whole-exome sequencing analysis, three RPE65 mutations were identified in two Japanese patients with LCA. This approach would be useful for identification of disease-causing mutations of LCA.