3,3'-Diindolylmethane (DIM), a small molecule compound, is a proposed Y preventive agent.

DIM is a potent radioprotector and mitigator that functions by stimulating an ATM-driven DDR-like response and NF-κB survival signaling. DIM can inhibit invasion, angiogenesis, and proliferation and induce apoptosis in tumor cells by modulating signaling pathways involving AKT, NF-κB, and FOXO3. It can also inhibit estrogen-inducible gene expression and cause an endoplasmic reticulum stress response. DIM alters estrogen metabolism by shifting metabolism from carcinogenic 16α-hydroxy to inert 2-hydroxy derivatives, and it antagonizes estrogen and androgen receptor activity[1].

Preliminary studies show DIM is most effective against total body irradiation (TBI) when given in multiple once-daily doses. Treatment of DIM has radioprotection and mitigation properties in vivo. DIM Activates ATM in Normal Tissues. DIM can be given to mice (250 mg/kg) by oral gavage, with no acute toxicity and excellent bioavailability[1].

The 184A1 and Hs578Bst cells are pretreated with DIM (0.3 μM) or vehicle for 24 h, irradiated by using different doses of 137Cs γ rays, harvested, plated at different densities, incubated for 14 d, and counted for colony formation.(Only for Reference)