Fundamental Toxicological Sciences

2022 - Vol. 9 No. 2

2022 - Vol. 9

Original Article
Potential human health risks of mercury-contaminated cassavas – Preliminary studies Vol.9, No.2, p.61-69
Sylvester Addai-Arhin , Randy Novirsa , Hui Ho Jeong , Quang Dinh Phan , Nana Hirota , Yasuhiro Ishibashi , Hideki Shiratsuchi , Koji Arizono
Released: April 27, 2022
Abstract Full Text PDF[1M]

The inevitable use of mercury (Hg) and the regular release of its waste into the ecosystem through artisanal and small-scale gold mining (ASGM) activities particularly, in developing countries such as Ghana require constant monitoring and evaluation of Hg contamination and its potential toxicities particularly, in samples such as food. This study evaluated the potential human health risks associated with total mercury (THg) and methylmercury (MeHg) levels of mercury-contaminated cassavas from farms in selected ASGM communities around Obuasi, Ghana. The THg and MeHg levels were evaluated using the direct Hg analyser, MA-3000 while the human health risk assessment was done using the USEPA risk assessment model. The estimated average daily intake for ingestion (eAvDI(ing)) (mg/kgbw/day) and the hazard quotient (HQ) for THg levels of the samples were above the USEPA reference values of 3 x 10−4 and 1, respectively. This means that residents ingest more Hg through consumption of cassava, hence long-term repeated exposures to the cassavas may be associated with detrimental human health effects in future. MeHg levels may not cause any human health effects due to eAvDI(ing) and HQ below 1 x 10−4 and 1, respectively. However, constant releases of mercury waste and subsequent bioaccumulation along the food chain can cause MeHg levels to increase with time above the USEPA acceptable daily intake. Such levels may be detrimental to human health. Therefore, there is the need for regular and strict monitoring of ASGM activities within the studied communities and other communities involved in ASGM to protect human health and preserve ecosystem integrity.

Relationship between micronucleus formation and oxidative stress in human vascular endothelial cells under low dose rate irradiation Vol.9, No.2, p.47-59
Qingmei Meng , Ikue Hayashi , Kumiko Anno , Junya Kobayashi
Released: April 05, 2022
Abstract Full Text PDF[2M]

Acute irradiation stimulates oxidative stress and DNA damage responses. However, it is unknown whether chronic irradiation (IR) at a low dose rate causes similar responses, and epidemiological studies of radiation-exposed people with low doses have reported effects on cardiovascular diseases. Therefore, we investigated the cellular effects under low dose rate of IR in human vascular endothelial cells as a model for cardiovascular diseases. We demonstrated that a low dose rate of IR induces phosphorylation of p38MAPK and STAT1, which is related to cGAS, and increases p21, a cellular senescence-regulatory factor. A low dose rate of IR also causes a remarkable formation of micronuclei in human vascular endothelial cells. DIA proteome analysis in human vascular endothelial cells indicated an increase in oxidative stress- and inflammation-related protein levels, and a decrease in protein levels related to the repression of micronuclei formation following exposure to low dose rate of IR. These results suggest that a low dose rate of IR might induce oxidative stress and micronuclei formation, which could activate the cGAS pathway and subsequently lead to cellular senescence.

Molecular network analysis of RNA viral infection pathway in diffuse- and intestinal-type gastric cancer Vol.9, No.2, p.37-46
Shihori Tanabe , Sabina Quader , Ryuichi Ono , Horacio Cabral , Kazuhiko Aoyagi , Akihiko Hirose , Hiroshi Yokozaki , Hiroki Sasaki
Released: April 05, 2022
Abstract Full Text PDF[4M]

There are several subtypes of gastric cancer, such as diffuse-type gastric cancer (GC) and intestinal-type GC. Diffuse-type GC is known to be more malignant than intestinal-type GC, showing high metastasis, recurrence and anti-cancer drug resistance. The malignant phenotype of diffuse-type GC includes cancer stem cell (CSC)-like features and epithelial-mesenchymal transition (EMT). By analyzing the molecular network in these tumors, it is possible to reveal the mechanisms of anti-cancer drug resistance, therapeutic targets and drug safety. Upon the analyses of the molecular network in diffuse- and intestinal-type GC, a regulatory network for RNA virus infection was obtained. This study aims to reveal the relationship between cancer and RNA virus infection in detail. RNA virus infection-related molecules and cancer-related molecules were analyzed using network analysis tools, such as Ingenuity Pathway Analysis (IPA), and molecular networks related to RNA virus infection mechanisms. Regulator effect analysis revealed the involvement of RNA virus infection network in diffuse-type GC. c-Jun N-terminal kinase (JNK) and BCL2 like 11 (BCL2L11) in the Coronavirus Pathogenesis Pathway were activated. In conclusion, this research suggested the relationship between the mechanisms of RNA virus infection and diffuse-type GC. This study may be useful for virus infection control and cancer drug discovery by clarifying the relationship between the mechanism of RNA virus infection and cancer.

Absence of in vivo mutagenicity of 4,4'-oxybis(benzenesulfonohydrazide) in liver and glandular stomach of MutaTM Mouse Vol.9, No.2, p.31-36
Takako Iso , Masakatsu Natsume , Yasumasa Murata , Yoshiyuki Shigeta , Nozomu Hirose , Takaaki Umano , Katsuyoshi Horibata , Kenichi Masumura , Kei-ichi Sugiyama , Mariko Matsumoto , Akihiko Hirose
Released: April 05, 2022
Abstract Full Text PDF[860K]

4,4'-Oxybis(benzenesulfonohydrazide) (OBSH) is a blowing agent widely used in the manufacture of porous plastics and rubber. OBSH was notified as an additive in the Japanese positive list system for food utensils, containers and packaging. The in vitro mutagenicity of OBSH was shown extensively in bacterial reverse mutation assays, a DNA repair test, and a chromosomal aberration test. Few studies exist on in vivo genotoxic evaluation on OBSH apart from an in vivo micronuclei test. To clarify in vivo mutagenicity, we conducted a transgenic rodent gene mutation (TGR) assay (OECD TG 488). We dosed male MutaTM Mouse with OBSH by oral gavage at 0 (negative control), 25, 50, and 100 mg/kg/day for 28 consecutive days, and evaluated mutant frequencies (MFs) of lacZ in the liver and glandular stomach (5 mice/group). We observed two deaths and a reduction in body weight at 100 mg/kg/day. Although we exposed MutaTM Mouse to OBSH orally for 28 days up to the maximum tolerated dose, we did not detect in vivo mutagenicity in the liver and glandular stomach. In contrast, in the positive control we detected significantly increased MFs. The results of this study suggest that OBSH is not mutagenic in vivo.