Hsu-Sheng Yu

Characteristics of aldehyde dehydrogenase 2 (Aldh2) knockout mice.

Acetaldehyde is an intermediate of ethanol oxidation. It covalently binds to DNA, and is known as a carcinogen. Aldehyde dehydrogenase 2 (ALDH2) is an important enzyme that oxidizes acetaldehyde. Approximately 45% of Chinese and Japanese individuals have the inactive ALDH2 genotypes (ALDH2*2/*2 and ALDH2*1/*2), and Aldh2 knockout mice appear to be a valid animal model for humans with inactive ALDH2. This review gives an overview of published studies on Aldh2 knockout mice, which were treated with ethanol or acetaldehyde. According to these studies, it was found that Aldh2 −/− mice (Aldh2 knockout mice) are more susceptible to ethanol and acetaldehyde-induced toxicity than Aldh2 +/+ mice (wild type mice). When mice were fed with ethanol, the mortality was increased. When they were exposed to atmospheres containing acetaldehyde, the Aldh2 −/− mice showed more severe toxic symptoms, like weight loss and higher blood acetaldehyde levels, as compared with the Aldh2 +/+ mice. Thus, ethanol and acetaldehyde treatment affects Aldh2 knockout mice more than wild type mice. Based on these findings, it is suggested that ethanol consumption and acetaldehyde inhalation are inferred to pose a higher risk to ALDH2-inactive humans. These results also support that ALDH2-deficient humans who habitually consume alcohol have a higher rate of cancer than humans with functional ALDH2.

Historical review on development of environmental quality standards and guideline values for air pollutants in Japan

Environmental quality standards (EQSs) have been established as desirable levels to be maintained for protection of human health and the conservation of the living environment by Basic Environment Law. EQSs in ambient air had been set for 10 substances (sulfur dioxide (SO(2)), carbon monoxide (CO), suspended particulate matter (SPM), nitrogen dioxide (NO(2)) and photochemical oxidants (Ox), benzene, tetrachloroethylene, trichloroethylene, dioxins and dichloromethane) and guideline values for 7 (acrylonitorile, vinyl chloride monomer, mercury, nickel compounds, 1,3-butadiene, chloroform and 1,2-dichloromethane) in Japan by 2009. EQSs for the classical (or traditional) air pollutants, SO(2), CO, SPM, NO(2) and Ox, were set according to the minimal requirement to protect human health, based on evidence from epidemiological studies conducted before the 1970s. In 1996, the Central Environment Council designated substances which may be hazardous air pollutants and substances requiring priority action, and adopted the concept of risk assessment to set EQSs and guideline values. A life-long risk level (virtually safe dose) of 10(-5) was used to set EQS for benzene, and guideline values for vinyl chloride monomer, nickel compounds, and 1,3-butadiene. EQSs for trichloroethylene, tetrachloroethylene and dichloromethane, and guideline values for acrylonitorile and mercury were set using uncertain factors and lowest observed adverse effect (LOAEL)/no observed adverse effect level (NOAEL). The results of animal experiments were utilized to set guideline values for chloroform and 1,2-dichloroethane. The benchmark approach and human equivalent concentration (HEC) were adopted for 1,2-dichloroethane. The history of setting EQSs and guideline values for hazardous air pollutants is one of adopting new concepts into risk assessment.

Polychlorinated biphenyls (PCBs) decrease the placental syncytiotrophoblast volume and increase Placental Growth Factor (PlGF) in the placenta of normal pregnancy

INTRODUCTION Polychlorinated biphenyls (PCBs) are a class of biologically active, highly stable compounds. Exposure risks include consumption of fatty fish, meat, dairy products and human breast milk, as well as environmental and occupational settings. Numerous reports have described PCB-dependent adverse effects on human fetal growth, including increased risk for IUGR, changes in endocrine function and hormone metabolism, and immunosuppressive and neurological deficits. Here we test the prediction that in utero PCB exposure adversely effects placental morphology, potentially leading to placental insufficiency en route to fetal growth restriction. METHODS PCB homologs (10) were measured in the maternal and fetal blood of a small cohort of normotensive pregnancies (22) by gas chromatography-mass spectrometry. PCB levels were compared with angiogenesis associated proteins Placental Growth Factor (PlGF) and sFlt-1, determined by ELISA, and the total estimated syncytiotrophoblast (ST) volume. RESULTS Significant associations between PCB exposure and both PlGF and ST volume were identified. DISCUSSION PCB effects on placenta morphology and predicted function are discussed. CONCLUSION These results demonstrate that the human placenta, including ST, is a target of PCB toxicity, and that current environmental PCB exposure levels are a risk to reproductive health.

The effect of ethanol on the formation of N 2-ethylidene-dG adducts in mice: implications for alcohol-related carcinogenicity of the oral cavity and esophagus

The present study aimed to experimentally confirm that long-term alcohol drinking causes a high risk of oral and esophageal cancer in aldehyde dehydrogenase 2 (ALDH2)-deficient individuals. Aldh2 knockout mice, an animal model of ALDH2-deficiency, were treated with 8% ethanol for 14 months. Levels of acetaldehyde-derived DNA adducts were increased in esophagus, tongue and submandibular gland. Our finding that a lack of Aldh2 leads to more DNA damage after chronic ethanol treatment in mice supports epidemiological findings on the carcinogenicity of alcohol in ALDH2-deficient individuals who drink chronically.