When lymphocytes are treated with corticosteroids, DNA analysis shows a ladder pattern on agarose gel. What is the most likely reason for this?

The appearance of a ladder pattern on an agarose gel following DNA analysis in lymphocytes treated with corticosteroids indicates DNA fragmentation, a hallmark of apoptosis. In this context, the correct answer relates to the regulation of apoptosis.

When corticosteroids are administered, they can lead to the activation of processes that favor cell survival by inhibiting apoptotic pathways. Specifically, activation of BCL2 plays a crucial role in this process because BCL2 is an anti-apoptotic protein that helps to prevent cell death by inhibiting the mitochondrial pathway of apoptosis. When there is a decrease in BCL2 activity, it results in increased apoptotic signaling, leading to the cleavage and fragmentation of the DNA, manifesting as a characteristic "ladder" pattern on agarose gel, indicative of the stepwise degradation of DNA during apoptosis.

Thus, the observation of the ladder pattern strongly correlates with the underperformance of pro-apoptotic signals and suggests an increased rate of apoptosis, directly linked to the inhibition of apoptotic pathways rather than activation or overexpression of other proteins, making the role of BCL2 particularly significant in this context.