Comparative Cr, As and CCA induced Cytostaticity in mice kidney: A contribution to assess CCA toxicity.

CCA (Chromium Copper Arsenate) treated wood, widely used in outdoor residential structures and playgrounds, poses considerable dangers of leaching of its components to the environment. In this study, mouse kidney samples were used to evaluate the effects of CCA, chromium trioxide (CrO3) and arsenic pentoxide (As2O5) on cell pathophysiology by flow cytometry. Samples were collected after 14, 24, 48 and 96 h of animal exposure. While Cr had no statistically significant cytostatic effects, As2O5 induced a S-phase delay in animals exposed for 24 h, and over time a G0/G1 phase blockage. The effects of CCA in S-phase were similar, but more severe than those of As2O5. Since environmental and public health hazards due to the long durability of CCA-treated wood products, these data confirm that CCA has profoundly toxic effects on cell cycle, distinct from the compounds themselves. These cytostatic effects support cell cycle dynamics as a valuable endpoint to assess the toxicity of remaining CCA-treated infrastructures, and the expected increased waste stream over the coming decades.

Nuclear Actin Is Required for Transcription during Drosophila Oogenesis.

Actin has been linked to processes spanning the whole gene expression cascade, from regulating specific transcription factors, such as myocardin-related transcription factor, to chromatin remodeling and RNA polymerase function. However, whether actin controls the transcription of only specific genes or has a global role in gene expression has remained elusive. Our genome-wide analysis reveals, for the first time, that actin interacts with essentially all transcribed genes in Drosophila ovaries. Actin co-occupies the majority of gene promoters together with Pol II, and on highly expressed genes, these two proteins also associate with gene bodies. Mechanistically, actin is required for Pol II recruitment to gene bodies, and manipulation of nuclear transport factors for actin leads to the decreased expression of eggshell genes. Collectively, these results uncover a global role for actin in transcription and demonstrate the in vivo importance of balanced nucleocytoplasmic shuttling of actin in the transcriptional control of a developmental process.

Mechanisms of kidney toxicity for chromium- and arsenic-based preservatives: potential involvement of a pro-oxidative pathway.

Metals have been extensively used for the preservation of wood. Among metallic conservatives, mixtures of chromated copper arsenate (CCA) were thoroughly used. However, the release and consequent mobilization of such compounds by biota, may culminate in the exertion of toxic chemical effects. The present study intended to show the toxicological effects caused by arsenic (7.2 mg/kg body weight), chromium (10.2 mg/kg Cr body weight) and the commercial mixture CCA (7.2 mg/kg As body weight and 10.2 mg/kg Cr body weight) in mice, namely the oxidative stress response (catalase - CAT, glutathione peroxidase - GPx, and glutathione-S-transferases - GSTs), in kidney tissues. The determination of the tested parameters was performed after exposure; organisms were exposed, and then sacrificed at two distinct periods, namely 14 and 96 h after the administration of toxicants. Exposure to chromium and arsenic induced significant modifications in the redox state of the test organisms, evidenced by significant alterations in GSTs and GPx activities. No alterations were found concerning the activity of catalase. These findings showed that the chemical mixture used as household product may exert significant toxicological outcomes in exposed animals, such as rodents, conditioning their redox homeostasis and antioxidant response.

Impairment of mice spermatogenesis by sodium arsenite.

In order to assess the effect of arsenic on the male reproductive impairment in mice, 7-week-old animals were exposed to 7.5 mg sodium arsenite (NaAsO(2))/kg body weight, during 35 days (one spermatogenic cycle). One group of animals was sacrificed after exposure, while another group received distilled water for an additional period of 35 days, in order to study the spermatoxic effect and the recovery of spermatogenesis. In mice sacrificed after NaAsO(2) exposure, a decrease in testis/body weight ratio and reduction of tubular diameter were observed. Both groups of NaAsO(2)-exposed animals showed remarkable histopathological changes, such as sloughing of immature germ cells. Animals sacrificed after NaAsO(2) exposure showed decreased sperm motility, increased abnormal sperm morphology and decreased sperm viability. The effects of NaAsO(2) on sperm motility recovered to normal values after one spermatogenic cycle, while increased sperm abnormality was maintained. However, at this period, a decrease in acrosome integrity was detected. Concerning oxidative stress parameters, animals sacrificed after NaAsO(2) exposure showed a decreased selenium-dependent glutathione peroxidase activity, which was not detected after the recovery. Conversely, at this period, total glutathione peroxidase activity increased in exposed animals. These results demonstrate the toxic effects of NaAsO(2) on mice spermatogenesis and show the lack of recovery after one spermatogenic cycle.

Nephrotoxicity effects of the wood preservative chromium copper arsenate on mice: histopathological and quantitative approaches.

Chromium copper arsenate (CCA) was used for the protection of wood building materials until the restriction by EPA in 2002. During a short period of time 14-24h, a comparative nephrotoxicity study was performed regarding the effects of CCA and its compounds per se. Histopathological and histochemical features were correlated with the concentration of the total arsenic and chromium in mice kidney. Animals were subcutaneously injected with CCA (7.2mg/kg arsenic and 10.2mg/kg chromium per body weight), CrO3 (10.2mg/kg), As2O5 (7.2 mg/kg) and NaCl (0.9%) per se. The histopathological examination of the renal sections evidenced acute tubular necrosis in the groups of animals exposed to CCA (in both periods of time). Although the same contents of pentavalent arsenic and hexavalent chromium were injected in treated animals with CCA and with the prepared solutions of As2O5 and CrO3, the arsenic concentration on kidneys of CCA-exposed animals was much higher than those in animals exposed to As2O5 (32- and 28-fold higher at 14 and 24h, respectively). However, the elimination of chromium seems to occur similarly in the kidneys of animals treated with CCA and CrO(3)per se. Interactions among the components of CCA result in a marked decrease of the ability of kidney to eliminate simultaneously both analytes. The nephrotoxicity of CCA was higher than its components per se, evidencing a possible synergetic effect.

Nephrotoxicity of CCA-treated wood: A comparative study with As(2)O(5) and CrO(3) on mice.

The purpose of this work was to assess the acute toxicity on male mice to a chromated copper arsenate (CCA) solution, a widespread wood preservative used in building industry until 2002. Animals were subcutaneously injected with CCA (7.2mg/kg arsenic and 10.2mg/kg chromium per body weight), CrO(3) (10.2mg/kg), As(2)O(5) (7.2mg/kg) and NaCl (0.9%) per se, during 48h and 96h, for histopathology, histochemistry, chromium and arsenic analysis. The results showed some histopathological changes within renal tubules lumen of CCA exposed animals (during 48h, and 96h), and CrO(3) (for the period of 96h). Furthermore, the renal levels of arsenic and chromium in treated animals were statistically more evident than controls. Although, the same contents of pentavalent arsenic and hexavalent chromium were injected into treated animals with CCA and with the prepared solutions of As(2)O(5) and CrO(3), a different distribution of the pattern of these compounds was observed in kidneys.