Integration of the rat liver micronucleus assay into a 28-day treatment protocol: testing the genotoxicity of four small-molecule nitrosamines with different carcinogenic potencies and tumor target specificities.

Several potent carcinogenic nitrosamines, including N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA), induce micronuclei in the micronucleated hepatocyte (MNHEP) assay but not in the micronucleated reticulocyte (MNRET) assay. However, the MNHEP assay is not as frequently used as the MNRET assay for evaluating in vivo genotoxicity. The present study evaluated MN formation in the liver of Big Blue transgenic rats exposed to four small-molecule nitrosamines, NDMA, N-nitrosodiisopropylamine (NDIPA), N-nitrosoethylisoporpylamine (NEIPA), and N-nitrosomethylphenylamine (NMPA), using a repeat-dose protocol typically used for in vivo mutagenicity studies.

Mutagenicity and genotoxicity evaluation of 15 nitrosamine drug substance-related impurities in human TK6 cells.

Nitrosamine drug substance-related impurities (NDSRIs) are a sub-category of N-nitrosamine drug impurities that share structural similarity to the corresponding active pharmaceutical ingredient. The mutagenicity of NDSRIs is poorly understood. We previously tested a series of NDSRIs using the Enhanced Ames Test (EAT).

Optimizing the detection of N-nitrosamine mutagenicity in the Ames test.

Accurately determining the mutagenicity of small-molecule N-nitrosamine drug impurities and nitrosamine drug substance-related impurities (NDSRIs) is critical to identifying mutagenic and cancer hazards. In the current study we have evaluated several approaches for enhancing assay sensitivity for evaluating the mutagenicity of N-nitrosamines in the bacterial reverse mutagenicity (Ames) test. Preincubation assays were conducted using five activation conditions: no exogenous metabolic activation and metabolic activation mixes employing both 10% and 30% liver S9 from hamsters and rats pretreated with inducers of enzymatic activity.

Pregnancy enhances antiviral immunity independent of type I IFN but dependent on IL-17-producing γδ T cells in the nasal mucosa.

Pregnancy is associated with profound changes in immunity. However, pregnancy-related respiratory immune adaptations in response to influenza infection and their impact on disease severity remain unclear. Here, we describe, in a preclinical model of mid-gestation pregnancy, a mechanism of enhanced host defense against influenza A virus (IAV) localized to the nasal cavity that limits viral replication and reduces the magnitude of intrapulmonary immune responses.

Brazilian Peppertree: Watch Out for This Lesser-Known Relative of Poison Ivy.

Brazilian peppertree (Schinus terebinthifolia), a member of the Anacardiaceae family, has invaded territory throughout the world, including the southeastern and western United States. Similar to fellow family members poison ivy and poison oak, Brazilian peppertree causes allergic contact dermatitis (ACD) in susceptible individuals. As this pest increases its range, dermatologists living in endemic areas should familiarize themselves with Brazilian peppertree, its effects on the skin, and how to treat any associated ACD.