Fundamental Toxicological Sciences

2014 - Vol. 1 No. 3

2014 - Vol. 1

Toxicomics Report
Identification of growth-dependent genes involved in paraquat toxicity in Saccharomyces cerevisiae Vol.1, No.3, p.113-114
Tsutomu Takahashi , JunXuan Zhu , Naoya Sonoda , Shusuke Kuge , Gi-Wook Hwang , Akira Naganuma
Released: November 10, 2014
Abstract Full Text PDF[379K]

Using the yeast strain library we established by overexpressing each gene essential for yeast growth, we comprehensively searched for genes affecting the sensitivity of yeast to paraquat. As a result, seven novel genes, UTP4, UTP25, SEC65, NDD1, TFB2, TIM23, and CCT6, were identified as conferring paraquat resistance in yeast via overexpression.

Toxicomics Report
Overexpression of RPN8, SKP1, MIA40 or MES1 increases resistance to cadmium in Saccharomyces cerevisiae Vol.1, No.3, p.109-111
Tsutomu Takahashi , JunXuan Zhu , Shusuke Kuge , Gi-Wook Hwang , Akira Naganuma
Released: November 10, 2014
Abstract Full Text PDF[301K]

We screened for genes associated with cadmium resistance among genes essential for cell growth in yeast. Four novel genes, RPN8, SKP1, MIA40 and MES1, were identified as genes providing cadmium resistance to yeast via overexpression.

Original Article
Sex-dependent difference in the hepatic and pulmonary toxicological effects in mice administrated 7-chlorinated benz[a]anthracene Vol.1, No.3, p.101-108
Hiroyuki Sakakibara , Takashi Ohura , Yuta Kamiya , Noriko Yamanaka , Nobuaki Shimada , Kayoko Shimoi , Keerthi S. Guruge
Released: November 10, 2014
Abstract Full Text PDF[288K]

Chlorinated polycyclic aromatic hydrocarbons (Cl-PAHs) have recently been found in the environment at relatively high concentrations. However, their toxicological information has not been well documented. In this study, a 24 hr in vivo experiment was conducted to evaluate the sex-dependent difference of the acute toxicological effects of 7-chlorinated benz[a]anthracene (7-ClBaA) as a model Cl-PAH. 7-ClBaA or its parent chemical, BaA, was once orally administered to male or female ICR mice at concentrations of 1, 10, and 100 mg/kg body weight. The relative liver weights of the males were significantly increased at the highest dose of both chemicals compared to the vehicle controls, but the weights were comparable among all groups in the females. The plasma 7-ClBaA level was similar in both sexes, but significantly higher than that of BaA. 7-ClBaA dose-dependently induced expression of the genes Cyp1a1, 1a2, and 1b1 in the liver and lung, and these stimulations were significantly higher in both organs and genders at a dose of 100 mg/kg 7-ClBaA compared with an equivalent amount of BaA, except in the case of hepatic Cyp1a2 and 1b1 and pulmonary Cyp1a2 in the female mice. The results suggest that acute toxicity of 7-ClBaA is gender- and organ-specific, and female mice might be less sensitive to acute toxicity of both 7-ClBaA and BaA than the males.

Original Article
A screening method for growth-dependent genes involved in the cytotoxicity of chemicals in Saccharomyces cerevisiae Vol.1, No.3, p.95-99
JunXuan Zhu , Tsutomu Takahashi , Shusuke Kuge , Gi-Wook Hwang , Akira Naganuma
Released: November 06, 2014
Abstract Full Text PDF[387K]

When considering mechanisms of toxicity development to chemical substances, one potentially important mechanism is the selective inhibition of proteins essential for cell growth (target molecules). In this study, to detect the target molecules of chemical substances, we established a method for comprehensively screening for essential proteins that confer resistance against chemical substances via overexpression in yeast. We used budding yeast, a common eukaryotic model organism, to produce yeast strains showing overexpression of different genes encoding essential proteins. This method was used to search for overexpressed genes conferring arsenite resistance in yeast, and as a result, we successfully identified ten types of new genes correlated with arsenite resistance.

Original Article
Residual metals in carbon nanotubes suppress the proliferation of neural stem cells Vol.1, No.3, p.87-94
Yukari Shigemoto-Mogami , Koki Fujimori , Yoshiaki Ikarashi , Akihiko Hirose , Yuko Sekino , Kaoru Sato
Released: November 06, 2014
Abstract Full Text PDF[236K]

Carbon nanotubes (CNTs) are used in many fields; however, little is known about the effects of CNTs on the central nervous system (CNS). In this study, we found that extracts of sonicated CNTs suppressed the proliferation of neural stem cells (NSCs). Single-walled CNTs (SWCNTs) and multiple-walled CNTs (MWCNTs) were suspended in PBS (1 mg/mL) and sonicated for 5 hr using a water bath sonicator. Supernatants from both types of CNTs suppressed NSC proliferation. The effects weakened in a dilution-ratio-dependent manner and strengthened in a sonication time-dependent manner. Metal concentrations extracted from SCNTs and MCNTs after 5-hr of sonication were determined using inductively coupled plasma mass spectrometry. Mn, Rb, Cs, Tl, and Fe were detected in the SWCNT supernatant, and Mn, Cs, W, and Tl were detected in the MWCNT supernatant. The concentration of Mn, Rb, and Fe eluted from the SWCNTs and Rb eluted from MWCNTs following sonication were sufficient to suppress NSC proliferation alone. N-acetyl cysteine (NAC) and ascorbic acid (AA) reversed the effects of Mn and Fe and restored NSC proliferation. The effects of Rb and Tl were not affected by the antioxidants. Both antioxidants largely restored the suppression of NSC proliferation induced by the SWCNT and MWCNT supernatants. These results suggest that metals extracted from CNTs via a strong vibration energy can suppress NSC proliferation through ROS production by the extracted metals.

Hazardous effects of titanium dioxide nanoparticles on testicular function in mice Vol.1, No.3, p.81-85
Nobuhiko Miura , Katsumi Ohtani , Tatsuya Hasegawa , Rieko Hojo , Yukie Yanagiba , Tetsuya Suzuki , Megumi Suda , Rui-Sheng Wang
Released: October 28, 2014
Abstract Full Text PDF[218K]

It has been reported that titanium dioxide nanoparticles (TiO2 NPs) show toxicity in organs such as liver, lung, and intestine. There is, however, only a limited number of reports regarding the effect of TiO2 NPs on the male reproductive system. We examined the effect of TiO2 NPs on testicular function using mouse model. TiO2 NPs (Aeroxide P25) were evenly dispersed in disodium phosphate solution by sonication. Mice were treated intravenously with TiO2 NPs (0, 2, or 10 mg/kg body weight) once per week for four weeks followed by sacrificing nine days after the last injection. The sperm head numbers and two sperm motion parameters, motile percent (MP) and progressive percent (PP), in the cauda epididymis were evaluated. TiO2 NPs significantly reduced the sperm head numbers in the cauda epididymis and testis, further, the motility ratios of both MP and PP. These results indicated that TiO2 NPs may possess hazardous effects on testicular function in mice.