Ginseng is one of the most widely taken herbal products in the world. The medicinal properties of ginseng have been linked to its antioxidative capability. Recently, use of herbal plants as possible modifiers of the radiation response has been receiving considerable attention. To explore the radioprotective potential of North American Ginseng Extract (NAGE), we conducted the cytokinesis-block micronuclei (MN) assay in human blood samples obtained from four healthy volunteers on the MN yield in peripheral blood lymphocytes (PBL) induced by 137Cs irradiation ex vivo. In this pilot study, we used standardized NAGE to the six major ginsenosides Rb1, Rb2, Rc, Rd, Re, and Rg1 at a level of 10.5% in total. NAGE was applied at three different time levels, i.e. 24 hr before irradiation, at 0 hr, and at 90 min after the irradiation. G0 PBL from each donor were incubated in medium containing different concentrations of NAGE (0, 50, 250, 500, and 1000 μg ml-1). PHA (1.5%, v/v) was added to the cultures immediately after 137Cs ex vivo irradiation (0 - 2 Gy, 0.6 Gy/min). Cytochalasin B (4μg ml-1) was applied at 44 hr after the PHA stimulation and cultures were terminated at the end of another 24 hr. The yield of MN in binucleated (BN) lymphocytes was determined by light microscopy on Hema-3 stained slides. We found that (1) at 0 Gy and without the presence of NAGE, MN yield (mean ± SEM) was 15.3 ± 1.1 per 1000 BN cells; different concentrations of NAGE applied at different time levels did not affect the MN yield (P = 0.3); (2) at different time levels, radiation alone increased MN 6 - 7 fold and 13.9 - 14.5 fold per 1000 BN cells linearly compared to the response at 0 Gy after 1 and 2 Gy exposures (P = 0.0001), respectively; and (3) MN yields declined linearly with the increasing NAGE concentration in PBL cultures exposed to either 1 Gy or 2 Gy at the three different time levels (P = 0.0001). NAGE applied at 24 hr before irradiation yielded the best radioprotective effects compared with radiation alone; at NAGE dose range of 50 - 1000 μg ml-1, the extent to which NAGE reduced the MN yield in PBL was 32% - 69.9% with 1 Gy exposure and 27.2% - 56% with 2 Gy exposures. Our data indicate that (1) NAGE at a concentration up to 1000 μg ml-1 incubated with human G0 PBL for 24 hr exerts no apparent adverse effect as evaluated by the MN yield; and (2) the unambiguous potential of NAGE to protect against 137Cs-induced MN in human G0 PBL ex vivo (1 - 2 Gy) is concentration-dependence at 24 hr before irradiation, at 0 hr, and even at 90 min after the irradiation. This work was supported by NIH/NCCAM grant R21AT002639–01A1.