Children with Cancer
This project sets out to fill the current knowledge gap about childhood cancer risks in association with maternal exposure to ambient air pollution, specifically particulate matter (PM), during pregnancy.
For this, the consortium will take the following steps:
- To determine the kinetics of transplacental transfer of PM samples, using our ex vivo human placenta dual perfusion system, PMs (obtained in collaboration with Topic 1) transferring from the maternal into the fetal circulation, will be detected in the foetoplacental circulation by means of advanced light and electron microscopy, following dual circuit perfusion of normal term placentas from recruited pregnancies in Manchester. Transferred PMs will be characterized according to their physicochemical properties.
- Foetal PM exposure will be determined by quantifying PM presence, again by using high end microscopy, in umbilical cord blood samples generated by the Born in Bradford mother-child birth cohort, in association with estimated maternal PM exposure during pregnancy. Whole genome gene expression analysis of cord blood cells will be applied to evaluate the impact of the foetal PM exposome on cancer signaling pathways related to prominent childhood cancers.
The outcomes of the project are:
- Providing proof-of-principle that airborne PM sampled from sites with varying traffic densities, is actually transferred across the human placenta;
- Providing proof-of-principle that foetal PM exposure actually takes place in association with maternal PM exposure, by demonstrating PM presence in umbilical cord blood samples from newborns;
- Providing proof-of-principle that foetal PM exposure induces genomic responses indicative of carcinogenic events.