Effects of generational low dose-rate Cs internal exposure in descendant mice.

To quantitatively investigate the effects of chronic low-dose internal exposure to Cesium-137 on DNA damage, carcinogenicity, and offspring over multiple generations. The potential genetic risk in humans was predicted based on next-generation murine mutation rates to confirm the reasonableness of the current Cesium-137 dose limits for food. Cesium-137 (100 Bq/mL) was provided in drinking water to A/J mice, facilitating chronic, low-dose, low-dose-rate internal exposure through sibling mating over 25 generations (G25).

Proximity effect of emergent field from spin ice in an oxide heterostructure.

Geometrical frustration endows magnets with degenerate ground states, resulting in exotic spin structures and quantum phenomena. Such magnets, called quantum magnets, can display non-coplanar spin textures and be a viable platform for the topological Hall effect driven by "emergent field." However, most quantum magnets are insulators, making it challenging to electrically detect associated fluctuations and excitations.

Oxidative stress accelerates intestinal tumorigenesis by enhancing 8-oxoguanine-mediated mutagenesis in MUTYH-deficient mice.

Oxidative stress-induced DNA damage and its repair systems are related to cancer etiology; however, the molecular basis triggering tumorigenesis is not well understood. Here, we aimed to explore the causal relationship between oxidative stress, somatic mutations in pre-tumor-initiated normal tissues, and tumor incidence in the small intestines of MUTYH-proficient and MUTYH-deficient mice. MUTYH is a base excision repair enzyme associated with human colorectal cancer.

Endogenous ROS production in early differentiation state suppresses endoderm differentiation via transient FOXC1 expression.

Oxidative stress plays a pivotal role in the differentiation and proliferation of cells and programmed cell death. However, studies on the role of oxidative stress in differentiation have mainly employed the detection of reactive oxygen species (ROS) during differentiation or generated by ROS inducers. Therefore, it is difficult to clarify the significance of endogenous ROS production in the differentiation of human cells.

Above-ordering-temperature large anomalous Hall effect in a triangular-lattice magnetic semiconductor.

While anomalous Hall effect (AHE) has been extensively studied in the past, efforts for realizing large Hall response have been mainly limited within intrinsic mechanism. Lately, however, a theory of extrinsic mechanism has predicted that magnetic scattering by spin cluster can induce large AHE even above magnetic ordering temperature, particularly in magnetic semiconductors with low carrier density, strong exchange coupling, and finite spin chirality. Here, we find out a new magnetic semiconductor EuAs, where Eu ions with large magnetic moments form distorted triangular lattice.

Characteristic mutations induced in the small intestine of Msh2-knockout gpt delta mice.

Background: Base pair mismatches in genomic DNA can result in mutagenesis, and consequently in tumorigenesis. To investigate how mismatch repair deficiency increases mutagenicity under oxidative stress, we examined the type and frequency of mutations arising in the mucosa of the small intestine of mice carrying a reporter gene encoding guanine phosphoribosyltransferase (gpt) and in which the Msh2 gene, which encodes a component of the mismatch repair system, was either intact (Msh2+/+::gpt/0; Msh2-bearing) or homozygously knockout (KO) (Msh2-/-::gpt/0; Msh2-KO).

Results: Gpt mutant frequency in the small intestine of Msh2-KO mice was about 10 times that in Msh2-bearing mice.

Oxidative-stress-driven mutagenesis in the small intestine of the gpt delta mouse induced by oral administration of potassium bromate.

Tumorigenesis induced by oxidative stress is thought to be initiated by mutagenesis, but via an indirect mechanism. The dose-response curves for agents that act by this route usually show a threshold, for unknown reasons. To gain insight into these phenomena, we have analyzed the dose response for mutagenesis induced by the oral administration of potassium bromate, a typical oxidative-stress-generating agent, to gpt delta mice.

Spontaneous de novo germline mutations in humans and mice: rates, spectra, causes and consequences.

Germline mutations are the origin of genetic variation and are widely considered to be the driving force of genome evolution. The rates and spectra of de novo mutations (DNMs) directly affect evolutionary speed and direction and thereby establish species-specific genomic futures in the long term. This has resulted in a keen interest in understanding the origin of germline mutations in mammals.

Feminizing endosymbiont disrupts maternal sex chromosome inheritance in a butterfly species.

is a maternally inherited ubiquitous endosymbiotic bacterium of arthropods that displays a diverse repertoire of host reproductive manipulations. For the first time, we demonstrate that manipulates sex chromosome inheritance in a sexually reproducing insect. butterfly females on Tanegashima Island, Japan, are infected with the Fem strain and produce all-female offspring, while antibiotic treatment results in male offspring.

Germline mutation rates and the long-term phenotypic effects of mutation accumulation in wild-type laboratory mice and mutator mice.

The germline mutation rate is an important parameter that affects the amount of genetic variation and the rate of evolution. However, neither the rate of germline mutations in laboratory mice nor the biological significance of the mutation rate in mammalian populations is clear. Here we studied genome-wide mutation rates and the long-term effects of mutation accumulation on phenotype in more than 20 generations of wild-type C57BL/6 mice and mutator mice, which have high DNA replication error rates.

PSMC5, a 19S Proteasomal ATPase, Regulates Cocaine Action in the Nucleus Accumbens.

ΔFosB is a stable transcription factor which accumulates in the nucleus accumbens (NAc), a key part of the brain's reward circuitry, in response to chronic exposure to cocaine or other drugs of abuse. While ΔFosB is known to heterodimerize with a Jun family member to form an active transcription factor complex, there has not to date been an open-ended exploration of other possible binding partners for ΔFosB in the brain. Here, by use of yeast two-hybrid assays, we identify PSMC5-also known as SUG1, an ATPase-containing subunit of the 19S proteasomal complex-as a novel interacting protein with ΔFosB.

8-oxoguanine causes spontaneous de novo germline mutations in mice.

Spontaneous germline mutations generate genetic diversity in populations of sexually reproductive organisms, and are thus regarded as a driving force of evolution. However, the cause and mechanism remain unclear. 8-oxoguanine (8-oxoG) is a candidate molecule that causes germline mutations, because it makes DNA more prone to mutation and is constantly generated by reactive oxygen species in vivo.

Mismatch repair deficient mice show susceptibility to oxidative stress-induced intestinal carcinogenesis.

We have previously established an experimental system for oxidative DNA damage-induced tumorigenesis in the small intestine of mice. To elucidate the roles of mismatch repair genes in the tumor suppression, we performed oxidative DNA damage-induced tumorigenesis experiments using Msh2-deficient mice. Oral administration of 0.

Nature of nontargeted radiation effects observed during fractionated irradiation-induced thymic lymphomagenesis in mice.

Changes in the thymic microenvironment lead to radiation-induced thymic lymphomagenesis, but the phenomena are not fully understood. Here we show that radiation-induced chromosomal instability and bystander effects occur in thymocytes and are involved in lymphomagenesis in C57BL/6 mice that have been irradiated four times with 1.8-Gy γ-rays.

NUDT16 and ITPA play a dual protective role in maintaining chromosome stability and cell growth by eliminating dIDP/IDP and dITP/ITP from nucleotide pools in mammals.

Mammalian inosine triphosphatase encoded by ITPA gene hydrolyzes ITP and dITP to monophosphates, avoiding their deleterious effects. Itpa(-) mice exhibited perinatal lethality, and significantly higher levels of inosine in cellular RNA and deoxyinosine in nuclear DNA were detected in Itpa(-) embryos than in wild-type embryos. Therefore, we examined the effects of ITPA deficiency on mouse embryonic fibroblasts (MEFs).

Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease.

It has been shown that molecular hydrogen (H(2)) acts as a therapeutic antioxidant and suppresses brain injury by buffering the effects of oxidative stress. Chronic oxidative stress causes neurodegenerative diseases such as Parkinson's disease (PD). Here, we show that drinking H(2)-containing water significantly reduced the loss of dopaminergic neurons in PD model mice using both acute and chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Construction and characterization of a cell line deficient in repair of mitochondrial, but not nuclear, oxidative DNA damage.

Oxidative base lesions, such as 8-oxoguanine, accumulate in nuclear and mitochondrial DNAs under oxidative stress, resulting in cell death. However, it is not known whether only oxidative lesion accumulated in mitochondrial DNA is involved in such cell death. By introducing human cDNA encoding a nuclear form of 8-oxoG DNA glycosylase (hOGG1-1a) into immortalized mouse embryo fibroblasts lacking Ogg1 gene, we established a cell line which selectively accumulates 8-oxoguanine in mitochondrial DNA under oxidative stress.

Quantitative analysis of oxidized guanine, 8-oxoguanine, in mitochondrial DNA by immunofluorescence method.

8-Oxoguanine (8-oxoG), an oxidized form of guanine, is one of the major mutagenic lesions generated under oxidative stress. Oxidative damage in mitochondrial DNA has been implicated as a causative factor for a wide variety of degenerative diseases as well as for cancer during aging. We established a quantitative method for in situ detection of 8-oxoG in mitochondrial DNA in a single-cell level using a monoclonal antibody.

Altered gene expression profiles and higher frequency of spontaneous DNA strand breaks in APEX2-null thymus.

A second class II AP endonuclease, APEX2, possesses strong 3'-5' exonuclease and 3'-phosphodiesterase activities but only very weak AP-endonuclease activity. APEX2 associates with proliferating cell nuclear antigen (PCNA), and the progression of S phase of the cell cycle is accompanied by its expression. APEX2-null mice exhibit severe dyslymphopoiesis in thymus as well as moderate dyshematopoiesis and growth retardation.

Two distinct pathways of cell death triggered by oxidative damage to nuclear and mitochondrial DNAs.

Oxidative base lesions, such as 8-oxoguanine (8-oxoG), accumulate in nuclear and mitochondrial DNAs under oxidative stress, resulting in cell death. However, it is not known which form of DNA is involved, whether nuclear or mitochondrial, nor is it known how the death order is executed. We established cells which selectively accumulate 8-oxoG in either type of DNA by expression of a nuclear or mitochondrial form of human 8-oxoG DNA glycosylase in OGG1-null mouse cells.

Oxidation of mitochondrial deoxynucleotide pools by exposure to sodium nitroprusside induces cell death.

Human MutT homolog (hMTH1) hydrolyzes oxidized purine nucleoside triphosphates to monophosphates, thereby avoiding incorporation of such oxidized purines into DNA or RNA. We examined whether hMTH1 prevents cellular dysfunction induced by sodium nitroprusside, a spontaneous NO donor. Exposure to sodium nitroprusside caused an 8-oxoguanine (8-oxoG) buildup in DNA of proliferating MTH1-null cells which underwent mitochondrial degeneration and subsequently died.

A genome-wide distribution of 8-oxoguanine correlates with the preferred regions for recombination and single nucleotide polymorphism in the human genome.

8-Oxoguanine (8-oxoG), a major spontaneous form of oxidative DNA damage, is considered to be a natural cause of genomic diversity in organisms because of its mutagenic potential. The steady-state level of 8-oxoG in the nuclear genome of a human cell has been estimated to be several residues per 10(6) guanines. In the present study, to clarify the genome-wide distribution of 8-oxoG in the steady state, we performed fluorescence in situ detection of 8-oxoG on human metaphase chromosomes using a monoclonal antibody.