Protective effects of Polyporus umbellatus polysaccharides alone and in combination with WR-2721 on radiation- and cyclophosphamide-induced genotoxicity in vitro and in vivo

[[abstract]]Polyporus umbellatus Polysaccharides (PUPs) are the main active components of Polyporus umbellatus, one of the commonly used traditional chinese medicines. In this study, the radioprotective and chemopreventive effects of PUPs were studied in vitro and in vivo. In human lymphoblastoid Tk6 cells, pretreatment of PUPs at a dose of 100 Ag/ml and 300 Ag/ml 30 min before irradiation significantly reduced radiation-induced micronuclei (MN) and tk mutant frequencies. Pretreatments of PUPs at a dose of 50 mg/Kg by i.p. injection 30 min or 45 min before 6 Gy irradiation resulted in statistically significant decrease of MN frequencies in the peripheral blood erythrocytes of irradiated mice. Comparative studies with a known radioprotective agent WR-2721 showed that PUPs may be a better radioprotective agent with a higher inhibition ratio of radiation-induced micronuclei and tk mutant frequencies. Mechanistic study showed that administration of PUPs at a dose of 50 mg/kg 30 min before irradiation significantly reduced the formation of the oxidative DNA damage (8-hydroxy-2V-deoxyguanosine) and lipid peroxidation in irradiated mouse liver. The antioxidant activity of PUPs may contribute to its radioprotective effect. Furthermore, PUPs caused a dose-dependent inhibition of cyclophosphamide-induced MN formation in TK6 cells. PUPs also inhibited MN frequencies in cyclophosphamide-treated mice. Since PUPs are natural, relatively nontoxic and less-expensive; these data suggest that PUPs may be a useful radioprotective agent and chemopreventive agent