Cellular DNA damage-related genes in association with in utero particulate matter exposure: p53 as a central hub

Abstract

Micronuclei (MN) are small nuclei, which are not incorporated in the daughter nuclei during cell division. They are formed as a result of chromosomal aberrations, and hence a valid biomarker for genotoxicity. DNA adducts and MN frequencies have been associated with in utero air pollution exposure in cord blood. Van Leeuwen et al. published a MN formation network with p53 as a central hub. The p53 gene encodes for the tumour suppressor protein which regulates incoming stress signals. We hypothesized that expression of genes involved in the MN formation network is altered in association with in utero PM2.5 exposure in newborns. Cord blood was retrieved from 96 newborns and gene expression of p53, DNMT1, PCNA, BAX and p21 was determined by qPCR. The key finding of this study was the positive association between in utero PM2.5 exposure during the first trimester of pregnancy and gene expression of p53 (3.21%, 95% CI: 0.41 to 0.61, p=0.03 for each 5 µg/m3 increase in PM2.5). In addition, expression of p53 was significantly associated with DNMT1 (r=0.26, p=0.01) and modestly associated with BAX (r=0.19, p=0.06) and PCNA (r=0.18, p=0.08). No significant association was found with gene expression of p21. Furthermore, we observed no direct significant association between PM2.5 exposure and the genes in the network individually, neither between PM2.5 exposure and the entire MN formation network, however a positive trend was observed.

Our results suggest that PM2.5 exposure affects p53 gene expression in cord blood. In this way,