Exploring the Role of Environmental Factors on Chromosomal Translocations Associated With Childhood Leukaemia.
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INTRODUCTION: Leukaemia is the most common cancer in children, with incidence rates increasing. Chromosomal translocations are considered one of the leukaemia-initiating events; however, the causes of many translocations remain unknown. Epidemiological studies have identified environmental exposures associated with altered risk of childhood leukaemia; however, there is little understanding of the molecular role they play in the aetiology of leukaemia. It is plausible that they contribute to the induction of translocations. METHODS: In this exploratory study, in vitro techniques were used to screen for the induction of translocations in response to environmental exposures suggested to be associated with childhood leukaemia risk that is, caffeine, benzene (smoking/air pollution), cotinine (smoking) and folate. Using physiologically relevant concentrations, NALM6 cells were exposed to each risk factor for up to 96 h. Reverse transcription PCR assays were used to detect common childhood leukaemia-associated translocations, TCF3::PBX1 and RUNX1::RUNX1T1. RESULTS: Preliminary experiments observed TCF3::PBX1 and RUNX1::RUNX1T1 translocations in benzene and cotinine exposed cells, including concentrations equivalent to passive smoke exposure. TCF3::PBX1 translocations were observed in caffeine-exposed cells at concentrations observed during pregnancy. TCF3::PBX1 and RUNX1::RUNX1T1 translocations were observed in cells grown in varying folic acid concentrations including levels within the normal physiological range. CONCLUSIONS: Our preliminary data provides proof of principle to suggest that environmental factors associated with childhood leukaemia risk have the potential to induce chromosomal translocations. Whilst this study is not designed to estimate in vivo risk or translocation frequency, it has allowed us to demonstrate a biologically plausible mechanism for epidemiological associations. Understanding the risk factors contributing to leukaemia-initiating events will be essential to refine public health policy and tailor prevention strategies.