In vivo genotoxicity assessment of a multiwalled carbon nanotube in a mouse ex vivo culture.

Background: Multiwalled carbon nanotubes (MWCNTs) are suspected lung carcinogens because their shape and size are similar to asbestos. Various MWCNT types are manufactured; however, only MWNT-7 is classified into Group 2B by The International Agency for Research on Cancer. MWNT-7's carcinogenicity is strongly related to inflammatory reactions.

Development of cisplatin resistance in breast cancer MCF7 cells by up-regulating aldo-keto reductase 1C3 expression, glutathione synthesis and proteasomal proteolysis.

Cisplatin (CDDP) is widely prescribed for the treatment of various cancers including bladder cancers, whereas its clinical use for breast cancer chemotherapy is restricted owing to easy acquisition of the chemoresistance. Here, we established a highly CDDP-resistant variant of human breast cancer MCF7 cells and found that procuring the resistance aberrantly elevates the expression of aldo-keto reductase (AKR) 1C3. Additionally, MCF7 cell sensitivity to CDDP was decreased and increased by overexpression and knockdown, respectively, of AKR1C3, clearly inferring that the enzyme plays a crucial role in acquiring the CDDP resistance.

The effect of aging on the repeated-dose liver micronucleus assay.

Background: The liver micronucleus (MN) assay is an effective and important in vivo test for detecting genotoxic compounds. In particular, the repeated-dose liver MN (RDLMN) assay which greatly facilitates incorporation of the liver MN assay into the general toxicity study has been developed. Usefulness of the RDLMN assay was appraised highly in the 7th International Workshops on Genotoxicity Testing (2017 in Tokyo) in that sufficient numbers and types of chemicals were studied and easy integration into the general toxicity study is preferred from the 3R's point of view.

Facilitation of 9,10-phenanthrenequinone-elicited neuroblastoma cell apoptosis by NAD(P)H:quinone oxidoreductase 1.

9,10-Phenanthrenequinone (PQ), a major quinone component in diesel exhaust particles, is considered to provoke damage of respiratory and vascular cells through highly producing reactive oxygen species (ROS), but little is known about its pathophysiological role in neuronal cell damage. In this study, we found that incubation with 1,2-naphthoquinone, 1,4-naphthoquinone and PQ, major quinone components in diesel exhausts, provokes apoptosis of human neuroblastoma cell lines. SK-N-SH cell treatment with a lethal concentration of PQ facilitated ROS production within 6 h.

Results of rat Pig-a/PIGRET assay with a single dose regimen of 1,3-propane sultone and 2-acetyl aminofluorene.

The Pig-a assay is a useful in vivo mutation detecting test and is easier to perform than the in vivo transgenic mutation assay. This assay is now recognized to be able to detect a number of mutagenic chemicals administered to rats in sub-acute or sub-chronic dose studies. The present investigation was conducted to evaluate the usefulness of peripheral blood Pig-a assays with total red blood cells (RBC Pig-a assay) and with reticulocytes (PIGRET assay) using two genotoxic rodent carcinogens, 1,3-propane sultone (1,3-PS) and 2-acetylaminofluorene (2-AAF).