Further studies on the potential contribution of acetaldehyde accumulation and oxidative stress in rat mammary tissue in the alcohol drinking promotion of breast cancer.

There is available evidence supporting a positive association between alcohol intake and risk of breast cancer. However, there is limited information regarding possible mechanisms for this effect. Past studies from our laboratory suggest that acetaldehyde accumulation in mammary tissue after alcohol intake may be of particular relevance and that cytosolic and microsomal in situ bioactivation of ethanol to acetaldehyde and free radicals and the resulting stimulation of oxidative stress could be a significant early event related to tumor promotion. In the present studies repetitive alcohol drinking for 28 days was found to produce significant decreases in the mammary tissue content of GSH and alpha tocopherol and in glutathione S-transferase or glutathione reductase activities. In contrast, glutathione peroxidase activity was slightly increased. Malondialdehyde determinations did not show the occurrence of lipid peroxidation while the xylenol orange procedure gave positive results. The mammary microsomal metabolism of ethanol to acetaldehyde was not induced after an acute dose of ethanol or acetone able to induce the activity of its liver counterpart. The cytosolic pathway of alcohol metabolism instead was significantly enhanced by these two treatments. No increased generation of comet images was found either in mammary tissue or in liver under the experimental conditions tested. Results suggest that, while acetaldehyde accumulation in mammary tissue could be a critical event resulting from increasing production of acetaldehyde in situ plus an additional amount of it arriving via blood, other factors such as poor handling of the accumulated acetaldehyde could be also relevant.

Liver nuclear and microsomal CYP2E1-mediated metabolism of xenobiotics in rats chronically drinking an alcohol-containing liquid diet.

In previous studies from our laboratory, the presence in highly purified liver nuclei of metabolic pathways for processing ethanol (EtOH), N-nitrosodimethylamine (NDMA), carbon tetrachloride and chloroform was reported. All these chemicals are known to be metabolized in liver microsomes, via cytochrome P450 2E1 (CYP2E)-mediated processes. In the present work we checked whether rat liver nuclei from rats chronically drinking an alcohol-containing liquid diet exhibited an enhanced ability to metabolize chemicals known to require CYP2E1 participation for given metabolic transformations. The nicotinamide adenosine dinucleotide phosphate (NADPH)-requiring metabolism of p-nitrophenol to p-nitrocathecol; the activation of carbon tetrachloride to trichloromethyl radicals, covalently binding to proteins; and the ring hydroxylation of aniline and o-toluidine were studied. Comparison of the obtained nuclear activities against the one present in the microsomal counterpart, and their respective response to the EtOH inductive effect after repetitive exposure to it, was studied. The obtained results showed that rat liver nuclei exhibited less p-nitrophenol hydroxylase activity than microsomes, but it was inducible by repetitive alcohol drinking to equivalent levels of those of microsomes from control animals. Nuclei exhibited the ability to activate CCl4, which was significantly enhanced by alcohol drinking. Aniline was ring hydroxylated in liver microsomes but not in nuclei from either control or EtOH-treated animals. In contrast, nuclei and microsomes metabolized o-toluidine to ring hydroxylated products. They are considered less toxic in nature but other authors reported a genotoxic effect for one of them. The production of the ring hydroxylated metabolites was enhanced by repetitive EtOH drinking. Results suggest that nuclear metabolism of xenobiotics might be relevant for either activations or detoxications mediated by CYP2E1 and that repetitive exposure to EtOH might significantly modulate those processes.

Rat liver microsomal and nuclear activation of methanol to hydroxymethyl free radicals.

Recent studies from other laboratories reported that during methanol intoxication lipid peroxidation and protein oxidation in liver occurred. Further, they detected free radicals-PBN adducts in bile and urine of methanol poisoned rats. In this work, we report the presence in liver microsomes and nuclei of NADPH dependent processes of hydroxymethyl (HMet) radical formation. The detection of HMet radicals was performed by GC/MS of the trimethylsilyl derivatives of the PBN (N-tert-butyl-a-phenylnitrone)-radical adducts. The formation of HMet radicals was observed only under nitrogen, in these in vitro conditions. Formation of formaldehyde from methanol was observed in aerobic incubation mixtures containing either microsomes or nuclei but also under nitrogen using microsomes. The latter process was not inhibited by diphenyleneiodonium while the anaerobic microsomal one producing HMet was strongly inhibited by it. This shows that they are independent processes. Results suggest that both, liver nuclei and microsomes are able to generate free radicals during NADPH-mediated methanol biotransformation.

Analisis del riesgo potencial para la salud y el medio ambiente derivado de la disposicion clandestina de agroquímicos en El Cuy, Provincia de Río Negro, Argentina / Environmental and health effects arising from two clandestine agrochemical waster buried in El Cuy, Río Negro (Argentina)

En el presente trabajo se exponen los resultados obtenidos de las pericias realizadas en la causa judicial originada en una denuncia por delitos contra el medio ambiente. La mismas conciernen al enterramiento clandestino de residuos de agroquímicos en un paraje semidesértico de la Provincia de Río Negro, Argentina. Un total de dieciocho muestras representativas de lo encontrado en las excavaciones se analizó por cromatografía gaseosa- espectrometría de masas (GC/MS). En todos los casos se constató la presencia de plaguicidas parcialmente degradados junto con sustanciaspropias de la formulación del producto técnico. En ninguno se observó la presencia de metales pesados. Por otra partese realizaron mediciones de residuos de plaguicidas sobre tierra de los pozoz y el área circundante, con el objeto de monitorear el proceso de limpieza y descontaminación del área (ánalisis de algunos plaguicidas organofosforados por GC con detección NOD). En base a datos geológicos e hidrográficos de la zona, se analizó el riesgo potencial para la salud y el medio ambiente

Analisis del riesgo potencial para la salud y el medio ambiente derivado de la disposicion clandestina de agroquímicos en El Cuy, Provincia de Río Negro, Argentina / Environmental and health effects arising from two clandestine agrochemical waster buried in El Cuy, Río Negro (Argentina)

En el presente trabajo se exponen los resultados obtenidos de las pericias realizadas en la causa judicial originada en una denuncia por delitos contra el medio ambiente. La mismas conciernen al enterramiento clandestino de residuos de agroquímicos en un paraje semidesértico de la Provincia de Río Negro, Argentina. Un total de dieciocho muestras representativas de lo encontrado en las excavaciones se analizó por cromatografía gaseosa- espectrometría de masas (GC/MS). En todos los casos se constató la presencia de plaguicidas parcialmente degradados junto con sustanciaspropias de la formulación del producto técnico. En ninguno se observó la presencia de metales pesados. Por otra partese realizaron mediciones de residuos de plaguicidas sobre tierra de los pozoz y el área circundante, con el objeto de monitorear el proceso de limpieza y descontaminación del área (ánalisis de algunos plaguicidas organofosforados por GC con detección NOD). En base a datos geológicos e hidrográficos de la zona, se analizó el riesgo potencial para la salud y el medio ambiente(AU)