<i>N</i>–nitrosodiethylamine cytochrome P450 induction and cytotoxicity evaluation in primary cultures of rat hepatocytes

The primary routes of potential human exposure to N-nitrosodiethylamine (NDEA) are ingestion, inhalation, and dermal contact. Air, diet and smoking contribute to potential human exposure at levels of a few μg of NDEA/day. Potential exposure depends on the ability of the nitrosamines to migrate from the product into the body. The first step in the metabolic degradation of NDEA by cytochrome oxidase (CYPs) enzymes is the introduction of a hydroxyl group and in human esophage and liver CYP2A3 and CYP2E1 participate on this metabolism. Measuring cytotoxicity in female rat primary hepatocytes cultures, were used to understand the CYP induction and metaboli-zation correlated with low NDEA concentrations. We observed that NDEA at different concentrations in the absence of CYPs inducers, was able to induce CYP2B1, CYP2B2, CYP2E1, CYP3A1 and CYP4A3. A positive NDEA synergistic effect on the levels of mRNA, was observed in the presence of pyrazole (300 μM) for CYP2B1 and CYP2B2 and for pregnenolone 16- carbonitrile (0.15 μM) for CYP2E1. Negative NDEA synergistic effects were observed for ethanol (0.3%) for CYP3A1, pyrazol (300 μM) for CYP2A1 and CYP2E1, and phenobarbital (1 mM) for CYP2A1. These facts are extremally important once that these metabolites can be directly related to the primary DNA lesions. We consider that studies to elucidate the biological factors that determine the shape of the dose-response curve are crucial for low-dose extrapolations of risk.

Preliminary Study by Environmental Indicator Measurements of Sediments in a Mangrove Forest in Ilha Grande Bay,Rio de Janeiro,Southeastern Brazil

Mangroves perform essential functions in biological cycles and are protected by law in Brazil. However, they are being degraded above their support limit, leading to a reduction in the areas around the world. The area investigated in the present study is a potentially unpolluted mangrove ecosystem in the south of Rio de Janeiro state, Brazil. The aim of this work was to investigate the presence of metals and polycyclic aromatic hydrocarbons (PAHs) in mangrove sediment and to correlate them with mutagenic and genotoxic activity. Four seasonal samplings undertaken between 2009 and 2010 at five sites were analyzed. Dichloromethane extracts were obtained under sonication and subjected to mutagenicity assays using Salmonella microsuspension. Metal (Cd, Cr, Cu, Ni and Pb) contents were determined by atomic absorption spectrometry, while the quantification of PAHs was performed by gas chromatography-mass spectrometry. Goniopsis cruentata hemocytes were used to assess potential genotoxic damage (Micronucleus assay). The absence of mutagenicity was observed for all samples using Salmonella typhimurium strains TA97, TA98, TA100 and TA102, in the absence and presence of an exogenous mammalian metabolizing system. Among the metals, Cd and Cu were detected in autumn at values exceeding the threshold effect level and below the probable effect level. Benzo[a] pyrene was detected at levels above the threshold at one site, where small effects could be observed in the biota. Significant differences in the micronucleated cells observed suggest DNA damage had been induced by the PAHs identified.