Toxic exposures can cause DNA damage to cells on the other side of a placental trophoblast cell barrier (1). This may not occur directly because the toxins pass through the barrier, instead it can occur indirectly as a result of intercellular signalling within the toxin exposed barrier and a secondary release of DNA damaging molecules from the other side. This process shows similarities to the radiation-induced bystander effect. The mechanism, like that for the bystander effect, is not understood. Here we have explored whether this indirect DNA damage across the placental cell barrier might occur through a process of ‘abortive apoptosis’ when some of the features of apoptosis are exhibited, such as DNA fragmentation, but the cell does not die (2). To test this hypothesis we used BeWo cell barriers as a model of the placenta and human fibroblasts as bystander cells. The barriers were exposed to the DNA damaging reagents benzoquinone and hydroquinone to induce bystander signalling. The conditioned medium (CM) was collected on the other side of the barriers and was exposed to the fibroblasts. Caspase-3 (264155), caspase-6 (218757), caspase-8 (218840) and caspase-9 (218841) inhibitors (Merck Millipore) were applied either directly to the fibroblasts or indirectly to the barriers. The overall level DNA damage in arbitrary units was measured in the fibroblasts using the alkaline comet assay. The fibroblasts were also examined with live cell imaging for 72 hours after exposure to detect cell death. Values are means ± S.E.M., compared by Ttest. Fibroblasts showed no signs of apoptosis or death using live cell imaging after treatment with CM. They did show significant increased DNA damage (p<0.05 ). This was reduced by caspase-3 and -8 inhibitors (2.07 ± 0.559 and 2.16 ± 0.454 vs. 4.39 ± 0.476, respectively p<0.05). There was no significant change in DNA damage using caspase-9 inhibitor (5.24 ± 0.873 vs. 4.39 ± 0.476, p>0.05). An indirect application of the caspase inhibitors, on the barriers and not the fibroblasts, showed no change in levels of DNA damage for caspase-3 and -8 inhibitors (4.85 ± 1.30 and 3.55 ± 0.415 vs. 4.39 ± 0.476, respectively p>0.05) but there was a slight decrease of DNA damage with the caspase-6 and -9 inhibitors, but this wasn’t significant (2.92 ± 0.554 and 2.87 ± 0.669 vs. 4.39 ± 0.476, respectively p>0.05). These results suggest that the extrinsic pathway for apoptosis, which is known to cause DNA fragmentation via CAD, might play a role in this indirect DNA damage. This would be in keeping with the fibroblasts receiving a signal from the trophoblast barrier and with an abortive or perhaps incomplete form of apoptotic response. Caspase-6 is known to cause secretion of TNF-α (3) which is one of the putative radiation induced bystander signals (4) and which in our unpublished results is secreted from our BeWo barriers.