ABSTRACT: Palmitic acid, the most abundant fatty acid in the human diet, causes oxidative DNA damage, DNA strand breakage, necrosis, and apoptosis in human and rodent cells in vitro, while excess fatty acids in the diet increase the risk of colon cancer in vivo. Irradiation of palmitic acid leads to the formation of 2-dodecylcyclobutanone (2-DCB), a unique radiolytic product formed at part-per-million levels in fats. Recent research has raised the possibility that, like palmitic acid, 2-DCB can also cause DNA strand breaks in human and rodent cells. In order to more fully understand the clastogenic potential of 2-DCB, it was tested for the ability to induce the formation of micronuclei (MN) in human TK6 lymphoblasts. TK6 lymphoblasts were exposed to 13.3, 26.5, and 53 μM of 2-DCB for 24 h, both with and without exogenous metabolic activation (EMA). The number of MN per 1000 binucleated cells was induced 2.65-fold without EMA, and 2.85-fold in the presence of EMA at the highest 2-DCB concentration of 53 μM. Cytotoxicity of the TK6 lymphoblasts treated with 53 μM 2-DCB was 51.7% in the absence of EMA, and 61.7% in the presence of EMA. Thus, like palmitic acid, 2-DCB may be weakly clastogenic against human cells in vitro. Given the amount of 2-DCB that would be consumed when compared with that of its clastogenic parent fatty acid, 2-DCB is unlikely to have any significant impact on human health.