New Perspectives for Cancer Hazard Evaluation by the Report on Carcinogens: A Case Study Using Read-Across Methods in the Evaluation of Haloacetic Acids Found as Water Disinfection By-Products.

Background: Due to the large number of chemicals not yet tested for carcinogenicity but to which people are exposed, the limited number of human and animal cancer studies conducted each year, and the frequent need for a timely response, mechanistic data are playing an increasingly important role in carcinogen hazard identification.

Objectives: To provide a targeted approach to identify relevant mechanistic data in our cancer evaluation of haloacetic acids (HAAs), we used several approaches including systematic review, the 10 key characteristics of carcinogens (KCs), and read-across methods. Our objective in this commentary is to discuss the strengths, limitations, and challenges of these approaches in a cancer hazard assessment.

Health consequences of electric lighting practices in the modern world: A report on the National Toxicology Program's workshop on shift work at night, artificial light at night, and circadian disruption.

The invention of electric light has facilitated a society in which people work, sleep, eat, and play at all hours of the 24-hour day. Although electric light clearly has benefited humankind, exposures to electric light, especially light at night (LAN), may disrupt sleep and biological processes controlled by endogenous circadian clocks, potentially resulting in adverse health outcomes. Many of the studies evaluating adverse health effects have been conducted among night- and rotating-shift workers, because this scenario gives rise to significant exposure to LAN.

Effects of genistein on expression of bone markers during MC3T3-E1 osteoblastic cell differentiation.

In this in vitro study, the hypothesis that the beneficial effects of dietary genistein on bone are through the modulation of the bone marker synthesis by osteoblastic MC3T3-E1 cells was tested, and the possible roles of estrogen receptors in the actions of genistein on osteoblastic cells were also examined. Interleukin-6 production was decreased 40% to 60% in osteoblastic cells treated with genistein from either day 8-16 or day 12-16, at dietarily achievable concentrations (10(-10) to 10(-8) M) (P<0.05).

Soy isoflavones: no effects on bone mineral content and bone mineral density in healthy, menstruating young adult women after one year.

Background: The effects of isoflavone-enriched soy protein on human bone mineral content (mass) and density in healthy, menstruating young adult females have not been examined in a comparative prospective investigation. Peri- and post-menopausal women have been reported to show beneficial effects of isoflavones on bone measurements. Therefore, young women may also be able to improve their accrual of peak bone mineral content (BMC) and bone mineral density (BMD) during the early adult years of bone consolidation with an isoflavone-enriched diet.

Anabolic effects of a G protein-coupled receptor kinase inhibitor expressed in osteoblasts.

G protein-coupled receptors (GPCRs) play a key role in regulating bone remodeling. Whether GPCRs exert anabolic or catabolic osseous effects may be determined by the rate of receptor desensitization in osteoblasts. Receptor desensitization is largely mediated by direct phosphorylation of GPCR proteins by a family of enzymes termed GPCR kinases (GRKs).

A method for the determination of betaine in tissues using high performance liquid chromatography.

Betaine is a major metabolite of choline in liver and kidney and may be an important product of choline metabolism in other tissues. The available methods for assay of betaine, however, are time consuming and relatively insensitive. We describe a modification of published methods that provides a sensitive and specific assay for betaine by derivatization and HPLC separation with UV quantitation.