Vascular Aging and Disease of the Small Vessels.

Cardiovascular events are the consequence of vascular damage at both the macro and microcirculatory level. The relationship between large stiffening artery and microvascular disease may be bidirectional, since wave reflection from microvascular sites could increase systolic blood pressure and pulse pressure, while transmission of increased arterial pulsatility to microvessels could represent a mechanism of damage. Hypertension and aging share similar mechanisms of vascular dysfunction. In fact, vascular remodelling, endothelial dysfunction and vascular stiffness are common features in hypertension and aging. Structural and functional changes in small arteries occur during normal and accelerated aging, possibly triggered by hypertension. A cross-talk may be present between large and small artery changes, interacting with pressure wave transmission and reflection, exaggerating cardiac, brain and kidney damage, and finally leading to cardiovascular and renal complications.

New Methods to Study the Microcirculation.

Essential hypertension is associated with structural alterations in the microvessels; in particular, an increase in the media thickness to internal lumen ratio of small resistance arteries (MLR) and a reduction in capillary density have been observed. The evaluation of the morphological characteristics of small resistance arteries in humans is challenging. The gold-standard method is generally considered to be the measurement by wire or pressure micromyography of MLR of subcutaneous small vessels obtained by local biopsies. However, noninvasive techniques for the evaluation of retinal arterioles were recently proposed; in particular, 2 approaches, scanning laser Doppler flowmetry (SLDF) and adaptive optics (AO), seem to provide useful information. Both of them provide an estimation of the wall to lumen ratio (WLR) of retinal arterioles. Moreover, a noninvasive measurement of basal and total capillary density may be obtained by videomicroscopy/capillaroscopy. It has been recently demonstrated that AO has a substantial advantage over SLDF in terms of evaluation of microvascular morphology, since WLR measured with AO is more closely correlated with the M/L of subcutaneous small arteries. The possibility to noninvasively assess in a reliable way, microvascular morphology in a clinical setting may represent a major advancement, since micromyography has substantial limitations in its application due to the local invasiveness of the procedure.

Exposure to 915 MHz radiation induces micronuclei in Vicia faba root tips.

The increasing use of mobile phones and wireless networks raised a great debate about the real carcinogenic potential of radiofrequency-electromagnetic field (RF-EMF) exposure associated with these devices. Conflicting results are reported by the great majority of in vivo and in vitro studies on the capability of RF-EMF exposure to induce DNA damage and mutations in mammalian systems. Aimed at understanding whether less ambiguous responses to RF-EMF exposure might be evidenced in plant systems with respect to mammalian ones, in the present work the mutagenic effect of RF-EMF has been studied through the micronucleus (MN) test in secondary roots of Vicia faba seedlings exposed to mobile phone transmission in controlled conditions, inside a transverse electro magnetic (TEM) cell. Exposure of roots was carried out for 72h using a continuous wave (CW) of 915 MHz radiation at three values of equivalent plane wave power densities (23, 35 and 46W/m(2)). The specific absorption rate (SAR) was measured with a calorimetric method and the corresponding values were found to fall in the range of 0.4-1.5W/kg. Results of three independent experiments show the induction of a significant increase of MN frequency after exposure, ranging from a 2.3-fold increase above the sham value, at the lowest SAR level, up to a 7-fold increase at the highest SAR. These findings are in agreement with the limited number of data on cytogenetic effects detected in other plant systems exposed to mobile phone RF-EMF frequencies and clearly show the capability of radiofrequency exposure to induce DNA damage in this eukaryotic cell system.

Ground and surface water for drinking: a laboratory study on genotoxicity using plant tests.

ABSTRACT: Surface waters are increasingly utilized for drinking water because groundwater sources are often polluted. Several monitoring studies have detected the presence of mutagenicity in drinking water, especially from surface sources due to the reaction of natural organic matter with disinfectant. The study aimed to investigate the genotoxic potential of the products of reaction between humic substances, which are naturally present in surface water, and three disinfectants: chlorine dioxide, sodium hypochlorite and peracetic acid. Commercial humic acids dissolved in distilled water at different total organic carbon (TOC) concentrations were studied in order to simulate natural conditions of both ground water (TOC=2.5 mg/L) and surface water (TOC=7.5 mg/L). These solutions were treated with the biocides at a 1:1 molar ratio of C:disinfectant and tested for genotoxicity using the anaphase chromosomal aberration and micronucleus tests in Allium cepa, and the Vicia faba and Tradescantia micronucleus tests. The tests were carried out after different times and with different modes of exposure, and at 1:1 and 1:10 dilutions of disinfected and undisinfected humic acid solutions. A genotoxic effect was found for sodium hypochlorite in all plant tests, at both TOCs considered, while chlorine dioxide gave positive results only with the A.cepa tests. Some positive effects were also detected for PAA (A.cepa and Tradescantia). No relevant differences were found in samples with different TOC values. The significant increase in all genotoxicity end-points induced by all tested disinfectants indicates that a genotoxic potential is exerted even in the presence of organic substances at similar concentrations to those frequently present in drinking water.

Modulation of cytochrome P450 and induction of DNA damage in Cyprinus carpio exposed in situ to surface water treated with chlorine or alternative disinfectants in different seasons.

Epidemiological studies have shown an association between consumption of disinfected drinking water and adverse health outcomes. The chemicals used to disinfect water react with occurring organic matter and anthropogenic contaminants in the source water, resulting in the formation of disinfection by-products (DBPs). The observations that some DBPs are carcinogenic in animal models have raised public concern over the possible adverse health effects for humans. Here, the modulation of liver cytochrome P450-linked monooxygenases (MFO) and the genotoxic effects in erythrocytes of Cyprinus carpio fish exposed in situ to surface drinking water in the presence of disinfectants, such as sodium hypochlorite (NaClO), chlorine dioxide (ClO(2)) and peracetic acid (PAA), were investigated in winter and summer. A complex induction/suppression pattern of CYP-associated MFOs in winter was observed for all disinfectants. For example, a 3.4- to 15-fold increase was recorded of the CYP2B1/2-linked dealkylation of penthoxyresorufin with NaClO (10 days) and PAA (20 days). In contrast, ClO(2) generated the most notable inactivation, the CYP2E1-supported hydroxylation of p-nitrophenol being decreased up to 71% after 10 days' treatment. In summer, the degree of modulation was modest, with the exception of CYP3A1/2 and CYP1A1 supported MFOs (62% loss after 20 days PAA). The micronucleus (MN) induction in fish circulating erythrocytes was also analysed as an endpoint of genotoxic potential in the same fish population. Significant increases of MN induction were detected at the latest sampling time on fish exposed to surface water treated with chlorinate-disinfectants, both in winter (NaClO) and summer (NaClO and ClO(2)), while no effect was observed in fish exposed to PAA-treated water. These results show that water disinfection may be responsible for harmful outcomes in terms of MFO perturbation and DNA damage; if extrapolated to humans, they ultimately offer a possible rationale for the increased urinary cancer risk recorded in regular drinking water consumers.

Modulating effects of humic acids on genotoxicity induced by water disinfectants in Cyprinus carpio.

The use of chlorinated disinfectants during drinking-water production has been shown to generate halogenated compounds as a result of interactions of humic acids with chlorine. Such chlorinated by-products have been shown to induce genotoxic effects and consumption of chlorinated drinking-water has been correlated with increased risk for cancer induction in human populations. The aim of this work was to test the potential genotoxic effects on circulating erythrocytes of the fish Cyprinus carpio exposed in vivo to well-waters disinfected with sodium hypochlorite (NaClO), chlorine dioxide (ClO2) or peracetic acid (CH3COO2H, PAA), in the absence or presence of standard humic acids (HA). The effects were measured by use of the micronucleus (MN) and the single-cell gel electrophoresis (Comet) assays at different sampling times after a 3-day exposure period. The exposure to chlorine disinfectants without the addition of HA produced a clear toxic effect. Significant cytogenetic damage (i.e. MN induction) was detected in fish populations exposed to both NaClO and ClO2 with humic acids. In the Comet assay, a significant decrease of DNA migration was observed in erythrocytes of specimens after exposure to NaClO-disinfected water without HA. No effects were observed in any other experimental condition.

Genotoxicity of drinking water disinfectants in plant bioassays.

The genotoxicity of two widely used drinking water disinfectants, sodium hypochlorite (NaClO) and chlorine dioxide (ClO(2)), and a new disinfectant, peracetic acid (PAA, CH(3)-CO-COOH), was evaluated in three short-term plant tests: (1) induction of anaphase chromosome aberrations in the root cells of Allium cepa, (2) micronucleus induction in the root cells of Vicia faba, and (3) micronucleus induction in Tradescantia pollen cells. The study was carried out in the laboratory by directly exposing the plants to several concentrations of the disinfectants in redistilled water at unadjusted (acid) and adjusted (neutral) pHs. Both 0.1 and 0.2 mg/l NaClO induced chromosome aberrations in the Allium cepa test at acid pH, but concentrations up to 0.5 mg/l of all the disinfectants were negative at neutral pH. Concentrations ranging from 0.1 to 0.5 mg/l NaClO, ClO(2,) and PAA induced micronuclei in Vicia faba at acid pH, while 1-2 mg/l NaClO and ClO(2) and 0.5-2 mg/l PAA gave positive responses at neutral pH. Most of concentrations of ClO(2) produced positive responses in the Tradescantia micronucleus test. In general, the highest levels of genotoxicity were observed under acid conditions; at acid pH, significant effects were induced by low concentrations of ClO(2) and PAA. Since the test concentrations of disinfectants are typical of those encountered in the biocidal treatment of tap water and similar concentrations are consumed daily by a large number of people, the genotoxicity of these compounds may constitute a significant public health concern.