Caffeine exposure and folate deficiency in vitro can influence chromosomal translocation events associated with childhood leukaemia.

Leukaemia accounts for a third of all childhood cancers, with many thought to originate from chromosomal rearrangements in utero. Various abnormalities, including chromosomal translocations, have been retrospectively detected at birth. Although survival rates are increasing, the incidence of childhood leukaemia has also been increasing each year. Epidemiological studies have identified various environmental factors associated with increased risk of childhood leukaemia including maternal nutrition, smoking and air pollution. It is plausible these exposures in utero and early childhood could trigger initiating translocations. Maternal nutrition such as caffeine intake and folate deficiency have been shown to influence adverse pregnancy outcomes, and in vitro exposure has been shown to affect DNA repair and cellular processes.

We aim to investigate if environmental exposures, such as caffeine and folate deficiency, associated with an increased risk of childhood leukaemia, may trigger the induction of translocations associated with childhood leukaemia.

To identify the optimal conditions for increasing susceptibility to translocations, the leukaemic cell line NALM6 was exposed to physiological levels of caffeine and folate deficiency. Cells were exposed to caffeine for 48 and 96 hours or grown in folate deficient media for 96 hours, before extracting RNA. Reverse transcription PCR assays developed to detect the most common childhood leukaemia associated translocations were used to identify translocation events.

Translocation events were seen at medium (10µM) levels of caffeine for 48 hours and very high levels of caffeine (80µM) for 96 hours. Induction of translocation events also occurred with depleted (1nM) and physiologically normal (10nM) levels of folate over 96 hours.

This data suggests environmental factors associated with childhood leukaemia may induce initiating translocations, suggesting a biologically plausible mechanism for epidemiological associations. With incidence rates rising, limiting these exposures could reduce translocations with the aim to preventing childhood leukaemia.

Thanks are given to Northumbria University and Children with Cancer UK for funding this project.