| Formaldehyde is a major chemical product, widely existence in the environment, and is a common air pollutant. In recent years, formaldehyde has been classified by WHO as carcinogen (A1level), and has made clear conclusion that formaldehyde can cause nasopharyngeal cancer, asthma and other diseases. US NTP organization has also considered formaldehyde leads to leukemia, but the mechanism how it causes toxicity of non-respiratory organs remains is unclear, particularly how it causes the toxicity of bone marrow cell is also worth to mark clear. In this study, the change of oxidative stress balance has been found related to the problem.1. The formaldehyde concentration in body influenced the toxicity of the Balb/c mice.Different concentrations formaldehyde solution which based the mouse body weight (6,12,18,30and60μg/g) was injected into the tail vein of mice, and then it was found that along with the formaldehyde concentration in the Balb/c mice is increased, the cells of organs can be found with a series of oxidative stress, while the oxidative injury was detected in the lung, liver, brain, kidneys, and bone marrow. The ROS (reactive oxygen species, ROS) level and oxidative damage were found increasing along with the rising in the concentration of formaldehyde in these organs except the lung. This phenomenon may relate to the fact that lung is a vital organ of the respiratory, organizational structure is different from others, so it has stronger tolerance against ROS. The malondialdehyde (malondialdehyde, MDA), is an important peroxidation product for membrane lipid, was found increased in the tissues and organs of the mice along with the injection of formaldehyde. When the injection concentration of formaldehyde reached at12μg/g, the MDA values of liver, lung, kidney and bone marrow cells reached to maximum. The DNA-protein cross-linking (DPC) in liver, lung, brain, kidney and bone marrow cells was also found increased at the formaldehyde levels of6～18μg/g (the highest DPC was at12μg/g), but decreased in the higher concentrations at30～60μg/g.These results indicate that:1) the trace quantities of formaldehyde generated in the body can lead to oxidative stress in body organs, which is a new discovery.2) Under the influence of trace formaldehyde, the body should have a formaldehyde response threshold. From our experimental results, the concentration of formaldehyde at12μg/g of the body may close to the threshold, triggering a chain reaction to change the balance of formaldehyde concentration in body. When injected formaldehyde concentration is increasing, the body can clear the adverse effects through the buffer and oxidative stress response elements, and then the body keeps formaldehyde rebalance.3) Further speculated that acute formaldehyde exposure can cause acute toxicity related reactions.2. The affect between Mice to Rats under the nose-mouth formaldehyde exposed. Exposed to the gaseous formaldehyde, whether rodents such as rats and mice, or primate rhesus monkey, etc., are all used to do the experiment, there is no confirmed which is the best kind of animal in toxicological experiments, and then no special model animals for gaseous formaldehyde exposured. The current international studies for gaseous formaldehyde exposure experiments, are most chosing the rat (for example Wistar rats) to carry out experiments, whereas use mice as animal models of formaldehyde toxicity studies is still relatively less. This study showed that using rats as animal model we have found the toxicity effects under exposure of3.0mg/m3gaseous formaldehyde. The biomarks in various organs of Wistar rats, particularly evident in the nasal cavity and the bone marrow can be positive detected compared with the control groups. The levels of reactive oxygen species (ROS) significantly increased, and the DPC also increased. As one of the biomarker of the antioxidant system, the reduced of glutathione (GSH) levels in the bone marrow, lung and spleen tissues were significantly decreased. These results indicated that3.0mg/m3formaldehyde exposure could induce oxidative damage on rat tissues and organs. Comparing to the nasal cavity, the bone marrow, lungs and spleen were not very sensitive (for example ROS, DPC changes did not obvious), but the changes of GSH could still be found. The same situations could be also found when Balb/c mice exposed to gaseous formaldehyde3.0mg/m3:in the nasal tissue and bone marrow (compared with the control group), the ROS and DPC index increased significantly and oxidative damage indicators corresponding GSH also decreased significantly; in lung and spleen tissues, the changes of ROS and DPC did not detected, but the GSH could still be detected a downward trend.By comparation of Wistar rats with Balb/c mice’s ROS, GSH and DPC, we can infer that, for gaseous formaldehyde exposure experiments, the rats and mice may have similar oxdative effects. During previous gaseous formaldehyde exposure experiments the rats were wildly used as subjects, with the present experiment that Balb/c mice had similar oxdative effects with rats’toxicological studies, we think mice can be a good alternative to rats for exposure experiments.3. Mouse bone marrow and other organ toxicity induced by formaldehyde exposure via nose-mouth inhalationIn this study, the experimental BALB/c mice were undertaken a short term and simulated occupational formaldehyde inhalation exposure (8h/d,7day), formaldehyde toxicity effects were detected on mouse bone marrow cells. ROS, MDA, GSH, DPC and other biomarkers have been used for testing formaldehyde induced oxidative damage on mouse bone marrow cells, according to100mg/kg body weight via gavage to mice injected, GSH was used for the establishment of formaldehyde toxicity suppression group. By RT-PCR detection, the formalydehy exposure to hematopoietic cells in the bone marrow had been found to play an important role in growth and differentiation of transforming growth factor (TGF-β) and hematopoietic growth factors (GM-Csf) during transcription; then the cell cycle changes were detected for bone marrow cells, and then bone marrow biopsy was undertaken to verify the pathological changes.Along with formaldehyde exposure concentration (0,0.5,1.0,3.0mg/m3) incresing, the biomarkers ROS, MDA and DPC values in lung, liver and bone marrow cells were significantly increased (P<0.01), and the value of GSH decreased (P<0.01); while the formaldehyde values of liver and bone marrow tissue were also increased (but lung tissue FA value does not change). The peripheral blood mononuclear cells in lymphoid almost no change for these biomakers. In GSH suppression group, the formaldehyde induced oxidative effects significantly reduced.The RT-PCR results also showed that, along with the formaldehyde concentration increasing, TGF-β and GM-Csf transcription also increased. The cell cycle detection of bone marrow cells and bone marrow biopsy also confirmed that the inhaled formaldehyde can really cause damage to bone marrow cells.Overall, these results suggst that formaldehyde can cause damage of bone marrow cells, as well as other organs cells. It can produce toxic effects via gene and cell cycle negative changes, suggesting high concentrations of formaldehyde exposure may increase the risk of leukemia. Of course, we still need more evidences to prove the relationship between formaldehyde and leukemia. |
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