Effects Of Formaldehyde Exposure On Methylation Of Lung,Liver And Brain Tissues In Mice

Formaldehyde is indoor air pollutant,which has been listed as A1 human carcinogen by the World Health Organization,but the carcinogenic mechanism of formaldehyde is still unknown.There are different views on its carcinogenic mechanism.Oxidative stress has long been considered to be involved in the pathophysiology of many human diseases,especially cancer.Some scholars believe that the imbalance of endogenous formaldehyde metabolism caused by exogenous formaldehyde exposure is considered to be the cause of formaldehyde-induced cancer.The metabolism of endogenous formaldehyde is associated with the metabolic pool of tetrahydrofolic acid in the body,which is related to the supply of one carbon unit of the body,such as methylation and demethylation.According to the theory that clinicopathological heterogeneity may be related to epigenetic destruction,we mainly used MSAP detection method from the perspective of epigenetics to explore the effect of formaldehyde on methylation level in different tissues of mice.The mice were divided into 5 groups:0 mg/m3FA group,0.5 mg/m3FA group,0.5 mg/m3FA+VE group,3.0 mg/m3FA group and 3.0 mg/m3FA+VE group.Eight mice in each group were exposed to gaseous formaldehyde for 8 hours a day for 14 days.The mice in 0.5 mg/m3 FA+VE group and 3.0 mg/m3 FA+VE group were intragastrically perfused with VE half an hour after each exposure.After two weeks of exposure,the mice were killed,and the lung,liver and brain tissues of the mice were taken to detect the level of oxidative stress,the concentration of formaldehyde in the tissue,the content of methyltransferase and the level of methylation.At the same time,the methylation patterns and states of different tissues under the same environmental stress were compared.The results showed that gaseous formaldehyde exposure caused different degrees of damage to different tissues.From the level of oxidative stress,we can see that the degree of oxidative damage caused by high concentration formaldehyde exposure is higher than that of low concentration formaldehyde exposure,but the degree of oxidative stress in different tissues is different.the oxidative stress level of lung tissue to formaldehyde exposure was higher than that of brain tissue and liver tissue.The analysis of the concentration of formaldehyde in different tissues showed that with the increase of the concentration of formaldehyde exposure,the concentration of formaldehyde in lung tissue increased significantly,while that in liver tissue decreased significantly,but it could hardly change the concentration of formaldehyde in brain tissue.We speculate that this result may be related to the functional differences of each organization.MSAP technique was used to detect the methylation status of genomic DNA in lung,liver and brain tissues of mice exposed to different concentrations of formaldehyde,and the differences of genomic DNA methylation levels in mice were also compared.After digested by Hpa Ⅱ/EcoR Ⅰ and Msp Ⅰ/EcoR I,it was found that the methylation degree of the same tissue was different after exposure to different concentrations of formaldehyde,indicating that gaseous formaldehyde exposure could change the methylation level and state of animal tissues.High concentration of formaldehyde increases the methylation level of lung,liver and brain tissue in varying degrees,low concentration formaldehyde does not affect the methylation level of lung tissue,but can cause hypermethylation of liver tissue and hypomethylation of brain tissue;in the same external environment,the methylation patterns of different tissue genomes are specific.Therefore,we think that the difference of methylation level between different tissues may be related to the expression of specific genes in different tissues.Lung tissue is the target organ of formaldehyde exposure,liver mitochondria have strong ability to oxidize formaldehyde,and brain tissue has blood-brain barrier.This may be the reason for the difference of methylation of formaldehyde to different tissues.From the results of the study,the metabolism of formaldehyde may be through oxidative stress,and the activity of DNMTs enzyme affects the level of DNA methylation.Under the same formaldehyde exposure stress,the methylation level of different tissues of mice can be changed,and the change of DNA methylation level is related to gene modification-methylation and demethylation,which will cause differences in the expression of many functional genes.This may be another experimental basis for formaldehyde-induced cancer.