DNA polymerase kappa counteracts inflammation-induced mutagenesis in multiple organs of mice.

In vitro studies indicate that DNA polymerase kappa (Polκ) is able to accurately and efficiently perform DNA synthesis using templates containing various types of DNA damage, including benzo[a]pyrene (BP)-induced N -deoxyguanosine adducts. In this study, we examined sensitivity of inactivated Polk knock-in (Polk ) mice to BP carcinogenicity in the colon by administering an oral dose of BP plus dextran sulfate sodium (DSS), an inflammation causing promoter of carcinogenesis. Although colon cancer was successfully induced by BP plus DSS, there was no significant difference in tumor incidence or multiplicity between Polk and Polk mice.

Method for Combined Observation of Serial Sections of Stented Arteries Embedded in Resin by Light Microscopy and Transmission Electron Microscopy.

We have developed a new method for obtaining information on whole tissues by light microscopy (LM) and ultrastructural features by transmission electron microscopy (TEM). This method uses serial sections of a stented artery embedded in resin. Stents were implanted in porcine coronary arteries in this study.

Effects of pregnancy experience on ovarian senescence and longevity in Hatano rats bred for high- and low-avoidance learning.

We investigated the effects of pregnancy experience on ovarian senescence and longevity using two inbred strains of Hatano rats. These strains have been selectively bred for high- and low-avoidance animals (HAA and LAA, respectively), but the HAA line has a slower onset of ovarian senescence and a shorter lifespan compared with the LAA line. The onset of abnormal estrous cycles and survival curves were compared between nulliparous and parous rats in each line.

Hatano rats selectively bred for high- and low-avoidance learning: an overview.

This review compiles the results of a series of studies on Hatano high- and low-avoidance animals (HAA and LAA, respectively) established at the Hatano Research Institute, Food and Drug Safety Center, Japan. The HAA and LAA lines were selected and bred from Sprague Dawley rats for high and low avoidance learning, respectively, in a shuttlebox task since 1985. Although Hatano rats were selected only based on their behavioral traits in the active avoidance task, strain differences between the HAA and LAA lines were also observed in their stress responses and reproductive functions.

The performance of an in vitro skin sensitisation test, IL-8 Luc assay (OECD442E), and the integrated approach with direct peptide reactive assay (DPRA).

In all current in vitro skin sensitisation assays, DMSO is used to dissolve water-insoluble chemicals. However, our previous study suggested the superiority of the modified IL-8 Luc assay (mIL-8 Luc), in which X-VIVO 15 is used to dissolve chemicals, over the original assay using DMSO (oIL-8 Luc). In this study, to confirm the superiority of the mIL-8 Luc, we first increased the number of chemicals examined and demonstrated the superiority of the mIL-8 Luc, in which the mIL-8 Luc provided 87.

Induction of a thoracolumbar supernumerary rib in rat developmental toxicity studies: A short discussion on the critical window.

Thoracolumbar supernumerary ribs (TSRs) are classified as less severe skeletal anomalies in rat developmental toxicity studies, although their incidence is relatively high in rodent studies. To investigate the characteristics of the critical window for chemically-induced TSR, in this study, rats were administered 5-fluorocytocine (5-FC) or sodium salicylate (SAL) at one of three time periods on gestational day (GD) 9, early morning (7:00 am), midday (12:00 pm to 1:00 pm), or late afternoon (4:00 pm or 7:00 pm). The incidence of TSR and other anomalies were assessed in GD20 fetuses.

Hatano rats are a suitable metabolic syndrome model for studying feeding behavior, blood pressure levels, and percent body fat.

Currently, metabolic syndrome is a worldwide concern. Thus, it is imperative to understand the mechanism of metabolic syndrome by establishing various metabolic syndrome models. In this study, we used Hatano high-avoidance animals (HAA) and low-avoidance animals (LAA), both derived from Sprague-Dawley rats by selective breeding to determine high- or low-avoidance rates in shuttle-box active avoidance tests.

Cause of and countermeasures for oxidation of the cysteine-derived reagent used in the amino acid derivative reactivity assay.

The amino acid derivative reactivity assay (ADRA) is an in chemico alternative to animal testing for skin sensitization that solves certain problems found in the use of the direct peptide reactivity assay (DPRA). During a recent validation study conducted at multiple laboratories as part of the process to include ADRA in an existing OECD test guideline, one of the nucleophilic reagents used in ADRA-N-(2-(1-naphthyl)acetyl)-l-cysteine (NAC)-was found to be susceptible to oxidation in much the same manner that the cysteine peptide used in DPRA was. Owing to this, we undertook a study to clarify the cause of the promotion of NAC oxidation.

Historical control data on developmental toxicity studies in rats.

Historical control data from prenatal developmental toxicity studies in rats have been used to evaluate whether toxicology outcomes were induced by exposure to a chemical or were within the range of spontaneous variation. These data are also important for monitoring animal characteristics. As a follow-up to historical control data from 1998 to 2010, this study analyzed control data from prenatal developmental studies performed in rats from 2011 to 2015.

Enhancement of Pesticide Peak Response in GC-MS in the Presence of Multiple Co-Existing Reference Pesticides.

We carried out a collaborative study in six laboratories to confirm the universality of the enhancing effect of co-existing reference pesticides on the GC-MS peak response to a target pesticide (malathion, procymidone, or flucythrinate). First, we confirmed the response enhancement of the target pesticides with increasing numbers of co-existing reference pesticides in solution. Then, using diluted green soybean matrix, we analyzed the target pesticides with two types of matrix-matched calibration, containing the target pesticides or 166 other pesticides.

Male Hatano low-avoidance rats show more active sexual behavior with lower plasma testosterone than high-avoidance rats.

Two inbred strains of Sprague-Dawley rats, known as the Hatano high- and low-avoidance animals (HAA and LAA respectively), have been selectively bred for high versus low rates of avoidance responses in a shuttle-box avoidance task. To investigate differences in the sexual behavior of Hatano rats, male HAA, LAA and SD rats were tested from 12 to 15 weeks of age. LAA rats exhibited more rapid and frequent sexual behavior than HAA or SD rats, and such differences increased with repeated sexual experience.

[Interlaboratory Study on Evaporation Residue Test for Food Contact Products (Report 2)].

An interlaboratory study was performed to evaluate the equivalence between an official method and a modified method of evaporation residue test using heptane as a food-simulating solvent for oily or fatty foods, based on the Japanese Food Sanitation Law for food contact products. Twenty-three laboratories participated, and tested the evaporation residues of nine test solutions as blind duplicates. In the official method, heating for evaporation was done with a water bath.

[Interlaboratory Study on Evaporation Residue Test for Food Contact Products (Report 1)].

An interlaboratory study was performed to evaluate the equivalence between an official method and a modified method of evaporation residue test using three food-simulating solvents (water, 4% acetic acid and 20% ethanol), based on the Japanese Food Sanitation Law for food contact products. Twenty-three laboratories participated, and tested the evaporation residues of nine test solutions as blind duplicates. For evaporation, a water bath was used in the official method, and a hot plate in the modified method.

Transferability and within- and between-laboratory reproducibilities of EpiSensA for predicting skin sensitization potential in vitro: A ring study in three laboratories.

The epidermal sensitization assay (EpiSensA) is an in vitro skin sensitization test method based on gene expression of four markers related to the induction of skin sensitization; the assay uses commercially available reconstructed human epidermis. EpiSensA has exhibited an accuracy of 90% for 72 chemicals, including lipophilic chemicals and pre-/pro-haptens, when compared with the results of the murine local lymph node assay. In this work, a ring study was performed by one lead and two naive laboratories to evaluate the transferability, as well as within- and between-laboratory reproducibilities, of EpiSensA.

Intravenous injection of artificial red cells and subsequent dye laser irradiation causes deep vessel impairment in an animal model of port-wine stain.

Our previous study proposed using artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment for port-wine stains (PWSs). Dye laser photons are absorbed by red blood cells (RBCs) and hemoglobin (Hb) mixture, which potentially produce more heat and photocoagulation and effectively destroy endothelial cells. Hb-Vs combination therapy will improve clinical outcomes of dye laser treatment for PWSs because very small vessels do not contain sufficient RBCs and they are poor absorbers/heaters of lasers.

Predictive performance and inter-laboratory reproducibility in assessing eye irritation potential of water- and oil-soluble mixtures using the Short Time Exposure test method.

The Short Time Exposure (STE) test method is an alternative method for assessing eye irritation potential using Statens Seruminstitut Rabbit Cornea cells and has been adopted as test guideline 491 by the Organisation for Economic Co-operation and Development. Its good predictive performance in identifying the Globally Harmonized System (GHS) No Category (NC) or Irritant Category has been demonstrated in evaluations of water-soluble substances, oil-soluble substances, and water-soluble mixtures. However, the predictive performance for oil-soluble mixtures was not evaluated.

Endocrine disrupting chemicals, 4-nonylphenol, bisphenol A and butyl benzyl phthalate, impair metabolism of estradiol in male and female rats as assessed by levels of 15α-hydroxyestrogens and catechol estrogens in urine.

Bisphenol A (BPA), 4-nonylphenol (NP) and butyl benzyl phthalate (BBP), termed endocrine-disrupting chemicals, are known to mimic estrogen activity. The effects of these chemicals on 17β-estradiol (E ) metabolism in vivo in rats were examined. Male and female rats were given NP (250 mg kg  day ), BPA (250 μg kg  day ) or BBP (500 mg kg  day ) by gavage for 14 days, followed by a single intraperitoneal injection of E (5 mg kg ) on the final day.

Alpha-1 antichymotrypsin is involved in astrocyte injury in concert with arginine-vasopressin during the development of acute hepatic encephalopathy.

Background And Aims: We developed a bio-artificial liver (BAL) using a radial-flow bioreactor and rescued mini-pig models with lethal acute liver failure (ALF). The point of the rescue is the recovery from hepatic encephalopathy (HE). HE on ALF has sometimes resulted in brain death following brain edema with astrocyte swelling.

Comparison of Assigned Values from Participants' Results, Spiked Concentrations of Test Samples, and Isotope Dilution Mass Spectrometric Results in Proficiency Testing for Pesticide Residue Analysis.

The Hatano Research Institute (HRI) at the Food and Drug Safety Center has recently organized a series of proficiency-testing (PT) programs called the "External Quality Control for Food Hygiene" in order to evaluate the analytical capability of testing laboratories that inspect food samples in accordance with the Food Sanitation Act. In one of these programs, Pesticide I, consensus values calculated from the participants' analytical results were used as assigned values, and the spiked concentrations of the prepared test samples were used for evaluating variation among individual participants. In the present study, the values obtained in the 2013-2015 rounds have been assessed by comparing the analytical results of the target pesticides obtained by using two different isotope-dilution MS (IDMS) methods.

Oral mucosal irritation study in hamster to evaluate a therapeutic apparatus using hydrogen peroxide photolysis for periodontitis treatment.

We conducted an oral mucosal irritation study in hamsters to evaluate a therapeutic apparatus using hydrogen peroxide (HO) photolysis for periodontitis treatment (ISO 10993-Part 10, Annex B.3). The cheek pouches in 15 male hamsters were allocated to one of six groups.

Genetic variation in low-dose effects of neonatal DES exposure in female rats.

To confirm genetic variation in low-dose effects of diethylstilbestrol (DES), two inbred strains of rats, which have been selectively bred for high- and low-avoidance learning (HAA and LAA, respectively), were used in this study. LAA rats characteristically show later sexual maturation, earlier reproductive senescence, and lower body weight as compared to HAA rats. Female neonates of each strain were daily administered DES by oral gavage at doses of 0 (vehicle only), 0.

Determination of urinary 15α-hydroxyestrogen levels via immunoaffinity extraction.

15α-Hydroxyestrogens (15α-OHEs) are metabolites of the female hormone estradiol. In this study, to discover physiological markers that can be utilized for monitoring fetal conditions and estrogen-induced cancers, we established a method for quantifying 15α-OHEs in rat urine via immunoaffinity column extraction and HPLC-electrochemical detection, and detected 15α-OHEs in urine obtained male rats treated with estradiol. Notably, the standard curves for quantification obtained using the column were linear over a range of 0.

Acute changes in histopathology and intravascular imaging after catheter-based renal denervation in a porcine model.

Objectives: We first aimed to identify the histopathological changes occurring immediately after renal denervation (RDN) with radiofrequency energy, and then to assess the feasibility of determining procedural success using currently available clinical intravascular imaging techniques.

Background: Catheter-based RDN has been used as an alternative therapy for hypertension. However, no practical endpoint to determine procedural success during treatment has been established.

Artificial Red Blood Cells as Potential Photosensitizers in Dye Laser Treatment Against Port-Wine Stains.

We suggest a novel method that uses artificial blood cells (hemoglobin vesicles, Hb-Vs) as photosensitizers in dye laser treatment (at 595-nm wavelength) for port-wine stains (i.e., capillary malformations presenting as red birthmarks) based on the results of animal experiments.

Photosensitizer Effects of Artificial Red Cells on Dye Laser Irradiation in an Animal Model Assuming Port-Wine Stain Treatment.

Background: The complete removal of port-wine stains has remained challenging. Based on the principle of treating port-wine stains with a dye laser, intravenous injection of artificial red cells (hemoglobin vesicles) immediately before laser treatment might improve the clinical outcome of the therapy. The hemoglobin vesicle injection increases the hemoglobin concentration in microvessels.