Leukaemia can arise from a single progenitor cell most likely during haematopoiesis, when there is a high degree of cellular proliferation. A sequence of molecular events is thought to disrupt the normal processes of differentiation and proliferation, generating a leukemic clone capable of expanding by indefinite self-renewal [1]. A two-hit model has been proposed for childhood leukaemia in which the first hit, an in utero exposure, transforms a haematopoietic stem cell (HSC) into a preleukaemic clone, and a second hit, postnatally, transforms this into a leukemic clone. Our work focuses mainly on prenatal exposures and environments that can cause post natal disease. Epidemiological studies demonstrate a link between childhood leukaemia and high birth weight. This may be caused by maternal growth hormones, such as insulin like growth factor-1 (IGF-1), which have a key role in feto-placental growth throughout gestation, and are positively correlated to birth weight [2]. IGF-1 also provides a potent stimulus for haematopoiesis. Therefore HSC’s in heavier babies might theoretically be exposed to increased proliferative stress resulting in an amplified likelihood of transformation. We have therefore examined whether IGF-1 may influence the level of DNA damage in cells which have been exposed indirectly to toxins on the other side of a model placental trophoblast cell barrier [3]. BeWo cells, a human trophoblast cell line, were grown as a confluent bilayered cell barrier on transwell inserts to create a model of the placental barrier. BeWo cells express type 1 IGF receptors but not insulin receptors and are therefore particularly useful [4]. Benzoquinone (BQ) and Hydroquinone (HQ) (30 uM) which are known to cause DNA damage and be associated with Leukaemia were placed in the upper chamber of the transwell inserts and human fibroblasts were placed in the lower chamber for 24 hours acting as a positive control as well as being mixed with IGF-1. The influence of IGF-1 (GroPep IU100) was tested above and below the trophoblast cell barrier. The level of DNA damage in the fibroblasts was recorded using the comet assay and with immunostaining of the histone protein H2AX as a marker of DNA double-stranded breaks (DSBs) [5]. BQ and HQ cause DNA damage to fibroblasts on the other side of the trophoblast barrier. IGF-1 appears to have two actions. It increases the level of DNA damage in unexposed fibroblasts in a dose dependant manner (50, 100 and 200 ng/mL, p=0.01, 0.005 and 0.001 respectively). It also acts to increase the level of DNA damage which is caused by the indirect exposure to hydroquinone and benzoquinone, again in a dose dependant manner (p=0.0005, 0.003, 0.0006). In conclusion our in vitro model establishes that IGF-1 has the potential to alter levels of DNA damage in cells exposed to toxin across a trophoblast cell barrier.