Fundamental Toxicological Sciences

2017 - Vol. 4 No. 1

2017 - Vol. 4

Toxicomics Report
Identification of transcription factors activated by methylmercury in mouse brain Vol.4, No.1, p.37-39
Min-Soek Kim , Tsutomu Takahashi , Jin-Yong Lee , Nobuhiko Miura , Masato Asanuma , Gi-Wook Hwang , Akira Naganuma
Released: February 24, 2017
Abstract Full Text PDF[329K]

Methylmercury is a harmful heavy metal that selectively disrupts the central nervous system. To clarify the transcription induction mechanism that operates in the brain in response to methylmercury exposure, we used a protein/DNA binding assay to identify transcription factors activated in the cerebella of mice administered methylmercury. We identified PAX4, PAX6, TCF3 and HMGA1 as transcription factors activated by methylmercury.

Toxicomics Report
Proteomic analysis of valproic acid-induced embryotoxicity in cultured post-implantation rat embryos Vol.4, No.1, p.31-35
Makoto Usami , Mina Takamatsu , Shugo Kazama , Katsuyoshi Mitsunaga , Atsuko Miyajima , Tomohiko Irie , Osamu Doi , Tatsuya Takizawa , Teruko Nagi , Momoko Sunouchi
Released: February 24, 2017
Abstract Full Text PDF[1M]

Protein expression changes were examined in day 10.5 rat embryos cultured for 24 hr in the presence of valproic acid (VPA), using two-dimensional electrophoresis and mass spectrometry. Exposure to VPA at an embryotoxic concentration of 1.2 mM resulted in quantitative changes in many embryonic protein spots (22 decreased and 29 increased). For the increased protein spots, 10 proteins were identified, including alpha-fetoprotein, phosphorylated cofilin-1, and serum albumin. These proteins are candidate protein biomarkers that may be involved in embryotoxic mechanisms.

Original Article
Application of a portable gas chromatograph for quantitative measurement of canine oral malodor Vol.4, No.1, p.23-29
Naoki Iwashita , Kazutoshi Sugita , Mitsuyuki Shirai , Sayaka Murata , Shiho Yanagisawa , Sumio Goto , Yukihiko Takagi , Fumitoshi Asai
Released: February 24, 2017
Abstract Full Text PDF[521K]

Oral malodor is an unpleasant condition experienced by most individuals around the world. Volatile sulfur compounds (VSCs) may be the main source of oral malodor both in humans and dogs. The purpose of this study was to examine the suitability for measurement of oral malodor levels in dogs using OralChromaTM, a portable gas chromatograph developed for human use. Oral malodor and periodontal disease in laboratory Beagle dogs (N = 6) were determined by organoleptic assessment and OraStrip® test, respectively. Relatively high concentrations of VSCs in the breath were detected in all six dogs in the order of hydrogen sulfide (H2S) > methyl mercaptan (CH3SH) > dimethyl sulfide ((CH3)2S). There was no significant influence of meals on VSCs levels. Significant correlations (P < 0.05) were observed among each VSC. These findings for the first time highlight the potential of OralChromaTM, which allows for noninvasive, rapid and quantitative measurement of oral malodor levels in dogs, and warrants further investigation.

Original Article
Normal ovarian aging, but modified T-cell differentiation, in female mice following neonatal exposure to bisphenol A Vol.4, No.1, p.15-21
Ryo Ohta , Hideo Ohmukai , Tsukasa Negura , Yoshiyuki Tazura , Omoko Shindo
Released: February 17, 2017
Abstract Full Text PDF[1M]

In a previous study, we found that early life exposure to low-dose diethylstilbestrol accelerated onset of abnormal estrous cycles in female C57BL/6J mice. In order to observe the ovarian aging of mice exposed to substances on the candidate list for endocrine-disrupting properties, neonates of C57BL/6J mice were orally administered bisphenol A (BPA) at doses of 5 and 50 μg/kg/day. As a result, normal ovarian aging was observed in females treated with BPA. However, females treated with 5 and 50 μg/kg/day of BPA showed modified T-cell differentiation in the thymus. These results suggested that early life exposure to low-dose BPA did not induce premature ovarian failure but modified T-cell differentiation in female mice.

Effects of oral administration of gelatin capsules on plasma insulin and glucagon levels in dogs Vol.4, No.1, p.9-14
Hideaki Yokoyama , Taku Masuyama , Tomio Ishida , Yusuke Suzuki , Toshiyuki Shoda , Hideyuki Kuno , Shoichiro Sugai
Released: February 08, 2017
Abstract Full Text PDF[377K]

A gelatin capsule is widely used as a device for oral administration of granular/powdered materials or small amounts of liquid materials in animal experiments. In this study, we investigated the insulin- and glucagon-related parameters following oral administration of gelatin capsules to beagle dogs since a gelatin capsule is made of protein composed of many amino acids as known to stimulate insulin or glucagon secretion. Gelatin capsules (1/2 ounces in size) were administered once orally to three male beagle dogs at the dose level of 0.29 and 1.67 g/kg as gelatin and the plasma levels of insulin, glucagon, glucose, non-esterified fatty acids (NEFA), total ketone bodies (KB) and alanine were determined before dosing and for up to 4 hr after dosing. Plasma insulin, glucagon and alanine levels increased immediately after dosing and subsequently plasma NEFA and total KB levels decreased. Most of these changes disappeared by 4 hr after dosing. No effects on plasma glucose levels were noted. In conclusion, a single oral administration of gelatin capsules increased plasma insulin and glucagon levels transiently and altered plasma levels of some biochemical parameters in dogs. These results might imply that attention should be paid to their own effect on the insulin and glucagon secretion at conducting animal experiments using a lot of gelatin capsules.

Original Article
Simultaneous depletion of WRNIP1 and RAD52 restores resistance to oxidative stress Vol.4, No.1, p.1-7
Akari Yoshimura , Haruna Yabe , Miho Akatani , Masayuki Seki , Takemi Enomoto
Released: January 27, 2017
Abstract Full Text PDF[1M]

WRNIP1 was originally identified as Werner (WRN) helicase interacting protein in a yeast two-hybrid screen. The WRN helicase, which is mutated in the progeroid disorder Werner syndrome, has been implicated in homologous recombination, DNA repair, and other DNA transactions. WRN also interacts with RAD52, which is conserved from yeast to human and may function in homologous recombination under certain conditions. In this study, we addressed the physical and functional relationship between WRNIP1 and RAD52. WRNIP1 and RAD52 formed a complex in cells. WRNIP1 and RAD52 double gene knockout cells grew slightly slower than each of the single gene knockout cell lines and wild-type cells, indicating that WRNIP1 and RAD52 are required to maintain the normal rate of cell growth. Interestingly, the sensitivity to hydrogen peroxide of each single gene knockout cell line was suppressed in double gene knockout cells, suggesting that a new pathway dealing with oxidative stress-induced DNA lesions operates in the absence of both WRNIP1 and RAD52.