Effects Of Traffic-Related Air Pollution Exposure On DNA Methylation And Histone H4K16 Acetylation

Objective The goal of the present study was to explore the effects of traffic-related air pollution exposure on DNA methylation and histone H4K16 acetylation.Methods 30 healthy Wistar rats were randomly divided into 5 groups of 6.The rats were then exposed to traffic-related air pollution at high(tunnel),moderate(crossroad)and low(control)pollution levels for 7d;two other groups were exposed in the tunnel for 14/28d.The levels of PM10 and NO2 were measured during the exposure.The study was performed in spring and autumn and the lung tissue and blood were collected after the exposure.Promoter methylation levels of p53、MGMT and MAGE-A4 were quantified by pyrosequencing;enzyme linked immunosorbent assay was used to measure the levels of histone H4K16 acetylation.Results The levels of PM10 and NO2 in the crossroad and tunnel group were significantly higher than that in the control group;the levels of PM10 and NO2 in autumn were nonsignificantly higher than that in spring.After 7d exposure in autumn,promoter methylation levels of p53(Pcrossroad<0.001;Ptunnel<0.001)and MGMT(Pcrossroad<0.001;Ptunnel=0.001)in lung tissue significantly decreased and the methylation status continued to decrease with increasing exposure time.MAGE-A4 was highly methylated and showed no difference in the three groups after 7d exposure;MAGE-A4 promoter methylation level in lung tissue significantly decreased after 14/28d exposure in the tunnel(P14d=0.008;P28d=0.003).Traffic-related air pollution exposure would not cause aberrant histone H4K16 acetylation.In lung tissue,;PM10 exposure was significantly associated with decreased p53 promoter methylation(r=-0.347,P=0.038)and increased histone H4K16 acetylation(r=0.448,P=0.010);NO2 exposure was significantly associated with decreased promoter methylation of p53,MGMT and MAGE-A4(r =-0.482、-0.444、-0.346,respectively;P<0.05)and increased histone H4K16 acetylation(r=0.448,P=0.010).In blood,PM10 and NO2 were significantly and positively associated with MAGE-A4 promoter methylation(r=0.395、0.431,respectively;P<0.05).Conclusions Traffic-related air pollution exposure would induce promoter hypomethylation of p53 and MGMT.