Environmental exposures influence chromosomal translocation events in 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. Causes of translocations are unknown, however chemotherapy drugs, such as the topoisomerase II poison, etoposide, can induce chromosome breaks and are associated with therapy related leukaemias.

Epidemiological studies have identified various environmental factors associated with increased risk of childhood leukaemia including smoking, maternal nutrition and air pollution. It is plausible these exposures in utero and early childhood could trigger initiating translocations. We aim to investigate if environmental exposures associated with an increased risk of childhood leukaemia, may trigger the induction of translocations associated with childhood leukaemia, utilising etoposide to increase translocation susceptibility.

To identify the optimal conditions for increasing susceptibility to translocations, the leukaemic cell line NALM6 was exposed for different lengths of time to various levels of etoposide and physiological levels of the selected environmental factors: benzene, cotinine, caffeine and folate. Reverse transcription PCR assays developed to detect the most common childhood leukaemia associated and etoposide related translocations were used to identify translocation events.

Preliminary results show exposure to high concentrations of etoposide for short periods of time, i.e. 1µM over a 1 hour exposure, can induce translocations. Different translocation events were seen for each environmental factor: at very high levels of caffeine (80µM) for 96 hours; for both benzene and cotinine concentrations similar to plasma levels observed in smokers and second-hand smoke exposure for 48-96 hours; and from depleted (1nM) to 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.