2-mercaptobenzothiazole generates γ-H2AX via CYP2E1-dependent production of reactive oxygen species in urothelial cells.

Ortho (o)-toluidine is a widely known carcinogenic substance associated with cancers of the human bladder. A study on British chemical factory workers exposed to 2-mercaptobenzothiazole, phenyl-β-naphthylamine, aniline, and o-toluidine demonstrated the crucial roles of o-toluidine, 2-mercaptobenzothiazole, and phenyl-β-naphthylamine in the development of bladder cancer. As genotoxic events are crucial steps in the initiation of cancer, in the present study, we aimed to examine the genotoxic potential of the four chemicals using phosphorylated histone H2AX (γ-H2AX), which is a sensitive and reliable marker of DNA damage, in cultured human urothelial cells.

Relationship between personal-sampled air lead and blood lead in low-lead-exposure workers in Japan to apply multiple regression models determining permissible air lead concentration.

Objectives: We investigated the relationship between lead in air (Pb-A) measured by personal sampling and blood lead (Pb-B) in workers with relatively low lead exposure to estimate the permissible air concentration of lead corresponding to the biological tolerance value of Pb-B of 15 µg/dL.

Methods: We collected air samples at a lead-acid battery factory in Japan by personal sampling devices attached to 32 workers (19 males and 13 females) and measured Pb-A by a graphite furnace atomic absorption spectrophotometer in 2017-2020. In addition, we collected information on age, smoking habits, Pb-B, and urinary δ-aminolevulinic acid from the records of medical examinations for lead poisoning.

Reassessment of the threshold of the blood lead level to increase urinary δ-aminolevulinic acid based on their relationship in recent lead workers in Japan.

Objectives: The present study investigated the quantitative relationship between blood lead (Pb-B) and urinary δ⁻aminolevulinic acid (ALA-U) in lead workers, and examined the Pb-B level that induces increases in ALA-U and the corresponding ALA-U.

Methods: We collected 10 562 data sets on Pb-B, ALA-U, age, and smoking habits from 808 workers (771 males and 37 females) who underwent multiple lead poisoning medical examinations at a lead-acid battery and lead smelting plant in Japan between 1995 and 2018. Females were excluded, and data collected in 169 subjects prior to engaging in lead work were used as the control.

Exposure Assessment of Cadmium in Female Farmers in Cadmium-Polluted Areas in Northern Japan.

Akita prefecture is located in the northern part of Japan and has many cadmium-polluted areas. We herein performed an exposure assessment of cadmium in 712 and 432 female farmers in two adjacent cadmium-polluted areas (A and B, respectively), who underwent local health examinations from 2001-2004. We measured cadmium concentrations in 100 food items collected from local markets in 2003.

Hospital-based screening to detect patients with cadmium nephropathy in cadmium-polluted areas in Japan.

Background: In health examinations for local inhabitants in cadmium-polluted areas, only healthy people are investigated, suggesting that patients with severe cadmium nephropathy or itai-itai disease may be overlooked. Therefore, we performed hospital-based screening to detect patients with cadmium nephropathy in two core medical institutes in cadmium-polluted areas in Akita prefecture, Japan.

Methods: Subjects for this screening were selected from patients aged 60 years or older with elevated serum creatinine levels and no definite renal diseases.

Acute exposure to cadmium induces prolonged neutrophilia along with delayed induction of granulocyte colony-stimulating factor in the livers of mice.

Acute exposure to cadmium (Cd), a toxic heavy metal, causes systemic inflammation characterized by neutrophilia. To elucidate the mechanism of neutrophilia induced by Cd, we investigated the induction of granulocyte colony-stimulating factor (G-CSF), which regulates neutrophil production, in mice with acute Cd toxicity, and compared it with mice injected with lipopolysaccharide (LPS) as an inducer of general inflammatory responses. We injected BALB/c mice with Cd at 2.

Suppression of erythropoietin induction by diethylstilbestrol in rats.

Diethylstilbestrol is an estrogenic endocrine disrupter that has diverse health effects in humans. Bisphenol A is another estrogen-like chemical with possible similar effects to diethylstilbestrol, which has been increasingly used for industry to lead to globally widespread human exposure to it. Hematopoiesis is another of their possible targets, since estrogen suppresses erythropoietin induction to induce anemia.

Age-relevant renal effects of cadmium exposure through consumption of home-harvested rice in female Japanese farmers.

There are cadmium-polluted areas in Japan, where farmers may be at risk of renal dysfunction due to cadmium exposure through consumption of home-harvested rice. The aims of this study were to investigate levels of cadmium exposure and accumulation and their renal effects in female farmers residing in cadmium-polluted areas, and to consider the relevance of age to the effects of cadmium. We conducted a cross-sectional study of 1200 women (40-79years old) without symptomatic disorders in two cadmium-polluted areas and one unpolluted area as a control.

Relationships between QT interval and heart rate variability at rest and the covariates in healthy young adults.

To clarify the links between ECG QT-related parameters and heart rate variability (HRV) and the covariates possibly distorting them, the averaged RR and QT intervals in a single lead ECG were measured for 64 male and 86 female subjects aged 18-26. The QT index, defined by Rautaharju et al., in the young adults was not significantly related to any HRV parameters nor heart rate, but the Bazett's corrected QT (QTc) interval was associated negatively with the parasympathetic activity and positively with heart rate.

[Current status of cadmium exposure among Japanese, especially regarding the safety standard for cadmium concentration in rice and adverse effects on proximal renal tubular function observed in farmers exposed to cadmium through consumption of self-grown rice].

Because the staple food in Japan is rice, which absorbs cadmium (Cd) from the soil efficiently, rice is the main source of exposure to Cd in the Japanese population. In addition, there have been many Cd-contaminated farming areas in Japan. Therefore, a safety standard for the Cd concentration in rice was set as 0.

Cadmium induces anemia through interdependent progress of hemolysis, body iron accumulation, and insufficient erythropoietin production in rats.

Cadmium is a toxic heavy metal and distributed widely in the environment. In addition to damaging the liver, kidneys, and bone, cadmium causes anemia through hemolysis, iron deficiency, and insufficient erythropoietin (EPO) production (renal anemia) along with changes in iron metabolism. Here, we investigated the role of iron in the interdependent progress of three types of anemia in cadmium-injected rats fed iron-sufficient or iron-deficient diets for 1 or 3 months.

[Application of the benchmark dose approach to epidemiological endpoints with clinical standards].

Objective: By publishing the scientific opinion entitled "Use of the benchmark dose (BMD) approach in risk assessment: Guidance of the Scientific Committee," the European Food Safety Authority (EFSA) recommended that the BMD approach, as an alternative to the traditionally used no-observed-adverse-effect level approach, be used as the method of choice for the determination of the reference point for deriving health-based guidance values and margins of exposure, and described the BMD approach as being extensively applicable to all chemicals, even to dose-effect assessment of epidemiological data. When the BMD approach was first proposed, the approach was expected to estimate the dose causing a low but measurable target organ effect. We examined whether the BMD approach can be applied to epidemiological endpoints with clinical standards.

Latest status of cadmium accumulation and its effects on kidneys, bone, and erythropoiesis in inhabitants of the formerly cadmium-polluted Jinzu River Basin in Toyama, Japan, after restoration of rice paddies.

Purpose: The cadmium-polluted Jinzu River Basin in Toyama, Japan, where nephropathy and itai-itai disease were endemic among resident farmers decades ago, has been almost completely restored. The aim of this study is to investigate whether inhabitants there would still exhibit cadmium accumulation and its effects on kidneys, bones, and erythropoiesis.

Methods: We performed a cross-sectional study of 150 subjects from the polluted area and 144 controls from the same prefecture.

Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells.

Phytoestrogens have attracted attention as being safer alternatives to hormone replacement therapy (HRT) and as chemopreventive reagents for breast cancer because dietary soy isoflavone intake has been correlated with reduction in risk. To identify safe and effective phytoestrogen candidates for HRT and breast cancer prevention, we investigated the effects of daidzein, genistein, coumestrol, resveratrol and glycitein on cell growth, cell cycle, cyclin D1 expression, apoptosis, Bcl-2/Bax expression ratio and p53-dependent or NF-kappaB-dependent transcriptional activity in MCF-7 breast cancer cells. Phytoestrogens, except for glycitein, significantly enhanced estrogen-response-element-dependent transcriptional activity up to a level similar to that of 17beta-estradiol (E(2)).

Gene expression signatures in peripheral blood cells from Japanese women exposed to environmental cadmium.

The objective of this study was to examine the effects of environmental cadmium (Cd) exposure on the gene expression profile of peripheral blood cells, using an original oligoDNA microarray. The study population consisted of 20 female residents in a Cd-polluted area (Cd-exposed group) and 20 female residents in a non-Cd-polluted area individually matched for age (control group). The mRNA levels in Cd-exposed subjects were compared with those in respective controls, using a microarray containing oligoDNA probes for 1867 genes.

[Anemia induced by cadmium intoxication].

Anemia is commonly induced by chronic cadmium (Cd) intoxication. Three main factors are involved in the development of Cd-induced anemia: hemolytic, iron-deficiency, and renal. Intravascular hemolysis can occur at the early stage of Cd exposure owing to the direct damaging effect on erythrocytes.

Dietary patterns associated with bone mineral density in premenopausal Japanese farmwomen.

Background: Because several nutrients are known to affect bone mineral density (BMD), the analysis of dietary patterns or combinations of foods may provide insights into the influence of diet on bone health.

Objective: We evaluated associations between dietary patterns and BMD in Japanese farmwomen.

Design: The study included 291 premenopausal farmwomen (aged 40-55 y) who participated in the Japanese Multi-centered Environmental Toxicant Study (JMETS; n = 1407).