4-Methylthio-3-butenyl isothiocyanate (MTBITC) induced apoptotic cell death and G2/M cell cycle arrest via ROS production in human esophageal epithelial cancer cells.

To investigate the chemopreventive mechanisms of 4-Methylthio-3-butenyl isothiocyanate (MTBITC), we analyzed cell viability, cell cycle distribution, and expression levels for cell cycle and apoptosis-related proteins in MTBITC-treated malignant esophageal KYSE510 cells, with and without the reactive oxygen species (ROS) scavenger N-acethyl-L-Cysteine (NAC). MTBITC dose-dependently reduced cell viability and Bcl2 protein expression, while it induced cleavages of caspase-3, caspase-9, and PARP-1, suggesting that reduced cell viability occurred through the mitochondrial apoptotic pathway in KYSE510 cells. In cell cycle distribution analysis, MTBITC (20-40 µM) induced cell cycle arrest at G2/M phase.

Regulation of NRF2, AP-1 and NF-κB by cigarette smoke exposure in three-dimensional human bronchial epithelial cells.

Cigarette smoke (CS) is a complex mixture of chemicals and interacts with various physiological processes. We previously reported that nuclear factor erythroid 2-related factor 2 (NRF2) was the most sensitive transcription factor to aqueous CS extract (AqCSE) exposure in monolayer cultured human bronchial epithelial cell lines. Recently, in vitro three-dimensional (3D) culture models have been used to supplement pharmacological and toxicological assessments.

4-Methylthio-3-butenyl isothiocyanate mediates nuclear factor (erythroid-derived 2)-like 2 activation by regulating reactive oxygen species production in human esophageal epithelial cells.

4-Methylthio-3-butenyl isothiocyanate (MTBITC) extracted from daikon (Raphanus sativus), which shows antimutagenicity, may have applications as an effective chemopreventive agent in several cancers; however, few reports have described the associated mechanisms. We investigated whether MTBITC induced cytoprotective genes, including phase II enzymes, in Het-1A human esophageal epithelial cells. HMOX1, NQO1, and GCLC mRNA levels and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein levels were increased in Het-1A cells treated with 10 μM MTBITC.

An environmental pollutant, 9,10-phenanthrenequinone, activates human TRPA1 via critical cysteines 621 and 665.

Transient receptor potential ankyrin 1 (TRPA1) is activated by noxious cold, mechanical stimulation, and irritant chemicals. In our recent study, 9, 10-phenanthrenequinone (9,10-PQ) is the most potent irritant for activation of NRF2 among 1395 cigarette smoke components and it may be, therefore, important to find its additional targets. Here, we show that 9,10-PQ functions as an activator of TRPA1 in human embryonic kidney (HEK) cells expressing human wild-type TRPA1 (HEK-wTRPA1) and human alveolar A549 (A549) cells.

Lack of in vivo mutagenicity of 1,2-dichloropropane and dichloromethane in the livers of gpt delta rats administered singly or in combination.

1,2-Dichloropropane (1,2-DCP) and dichloromethane (DCM) are possible causative agents associated with the development of cholangiocarcinoma in employees working in printing plant in Osaka, Japan. However, few reports have demonstrated an association between these agents and cholangiocarcinoma in rodent carcinogenicity studies. Moreover, the combined effects of these compounds have not been fully elucidated.

4-Methylthio-3-butenyl isothiocyanate (raphasatin) exerts chemopreventive effects against esophageal carcinogenesis in rats.

To examine the effects of 4-methylthio-3-butenyl isothiocyanate on esophageal carcinogenesis, male 6-week-old F344 rats were subcutaneously injected with 0.5 mg/kg body weight -nitrosomethylbenzylamine three times per week for 5 weeks and fed a diet supplemented with 80 ppm 4-methylthio-3-butenyl isothiocyanate, equivalent to 6.05 mg/kg body weight/day for the initiation stage, 4.

Toxic effects of 4-methylthio-3-butenyl isothiocyanate (Raphasatin) in the rat urinary bladder without genotoxicity.

We recently reported that 4-methylthio-3-butenyl isothiocyanate (MTBITC) exerts chemopreventive effects on the rat esophageal carcinogenesis model at a low dose of 80 ppm in a diet. In contrast, some isothiocyanates (ITCs) have been reported to cause toxic effects, promotion activity, and/or carcinogenic potential in the urinary bladder of rats. In the present study, we investigated whether MTBITC had toxic effects in the urinary bladder similar to other ITCs, such as phenethyl ITC (PEITC).

Activation of transcription factors in human bronchial epithelial cells exposed to aqueous extracts of mainstream cigarette smoke in vitro.

This study aimed to identify the most sensitive transcription factor activated by cigarette smoke extract (CSE) and to explore cigarette smoke components that have high biological activities in a cell-base assay. Previously, we found evidence that implicated 10 different transcription factors as having a high biological activity to CSE in vitro, based on the results of a comprehensive gene expression profile. For this study, luciferase reporter assays for each transcription factor were developed in two types of human bronchial epithelial cells: NCI-H292 and BEAS-2B cells.

Early Detection of Genotoxic Urinary Bladder Carcinogens by Immunohistochemistry for γ-H2AX.

DNA double-strand breaks (DSBs) induced by exposure to genotoxic agents are known to cause genome instability and cancer development. To evaluate the applicability of γ-H2AX, a sensitive marker of DSBs, in the early detection of genotoxicity and carcinogenicity of chemicals using animal models, we examined γ-H2AX expression in urinary bladders of rats. Six-week-old male F344 rats were orally treated for 4 weeks with a total of 12 chemicals divided into 4 categories based on genotoxicity and carcinogenicity in the urinary bladder.

Multiple episodic evolution events in V1R receptor genes of East-African cichlids.

Fish use olfaction to detect a variety of nonvolatile chemical signals, and thus, this sense is key to survival and communication. However, the contribution of the olfactory sense to social-especially reproductive-interactions in cichlids is still controversial. To obtain insights into this issue, we investigated the genes encoding V1Rs-possible candidates for reproductive pheromone receptors-among East-African cichlids.

Rapid and local autoregulation of cerebrovascular blood flow: a deep-brain imaging study in the mouse.

The brain obtains energy by keeping the cerebral blood flow constant against unexpected changes in systemic blood pressure. Although this homeostatic mechanism is widely known as cerebrovascular autoregulation, it is not understood how widely and how robustly it works in the brain. Using a needle-like objective lens designed for deep-tissue imaging, we quantified the degree of autoregulation in the mouse hippocampus with single-capillary resolution.

Novel multiwavelength microscopic scanner for mouse imaging.

Real-time in vivo imaging of molecular targets at (sub)cellular resolution is essential in better understanding complex biology. Confocal microscopy and multiphoton microscopy have been used in the past to achieve this goal, but their true capabilities have often been limited by bulky optics and difficult experimental set-ups requiring exteriorized organs. We describe here the development and validation of a unique near-infrared laser scanning microscope system that uses novel optics with a millimeter footprint.