Available online at www.sciencedirect.com Environmental Toxicology and Pharmacology 26 (2008) 80–85 Polysaccharides isolated from Ganoderma lucidum occurring in Southern parts of India, protects radiation induced damages both in vitro and in vivo Thulasi G. Pillai, Cherupally Krishnan Krishnan Nair, K.K. Janardhanan ∗ Amala Cancer Research Centre, Amalanagar, Thrissur, Kerala, India Received 21 September 2007; received in revised form 31 January 2008; accepted 5 February 2008 Available online 14 February 2008 Abstract The in vivo and in vitro radioprotective property of the polysaccharides isolated from Ganoderma lucidum were determined by survival studies, induction of micronucleus in reticulocytes of mice, strand breaks in plasmid pBR322 DNA and inhibition of lipid peroxidation (TBARS assay). Polysaccharides were administered as a single dose after whole body exposure to 10 Gy 60 Co -radiation to Swiss albino mice. At a dose of 500 g/kg body wt, the polysaccharides were most effective in protecting animals from radiation induced loss of lethality. Administration of 500 g/kg body wt to animal exposed to 10 Gy gamma radiation resulted in more than 60% survival on the 30th day compared to the dose of 300 mg/kg/body wt administration of amifostine, a clinically used radioprotective drug. The induction of micronuclei was reduced by the administration of polysaccharides. The decrease in micronuclei induction was dose dependent. Thus following 4 Gy exposure the micronuclei in polychromatic erythrocytes (MNCE) was reduced from 28.16 ± 3.049 to 16.0243 ± 2.074 and 6.30 ± 2.422 by polysaccharides at doses of 250 g/kg body wt and 500 g/kg body wt, respectively, and to 10.4 ± 2.581 by amifostine at a dose of 300 mg/kg body wt. The results indicate the significant protective effect of Ganoderma polysaccharides against radiation induced damages. The findings thus suggest the potential use of Ganoderma polysaccharides as novel radioprotective agent. © 2008 Elsevier B.V. All rights reserved. Keywords: Ganoderma lucidum; Polysaccharides; pBR 322; Micronucleus assay; Radioprotection; Lipid peroxidation 1. Introduction Ionizing radiation causes a variety of lesions in living cells which include damages to genomic DNA, the cellular vital tar- get and also oxidative damage to cellular macromolecules due to reactive oxygen species, mainly peroxidation of membrane lipids, protein oxidation and altered gene expression. The lesions in DNA produced by ionizing radiation are single and double strand breaks, DNA base damage, apyrimidinic/apurinic sites formation and inter and intra strand crosslinks and DNA protein crosslinks. The cellular responses include activation of certain cellu- lar signaling pathways particularly cytotoxic and cytoprotective pathways, (Schmidt-Ullrich et al., 2000) altered gene expres- sion (Hamasu et al., 2005). An unrepaired or misrepaired DNA damage can result in genetic or genomic instability, changes in ∗ Corresponding author. Tel.: +91 487 2307868; fax: +91 487 2307868. E-mail address: kkjanardhanan@yahoo.com (K.K. Janardhanan). cellular identity and function, cell death, and in multi-cellular organisms, neoplastic transformation. Eukaryotic cells have evolved efficient mechanisms to detect and repair DNA lesions induced within each phase of the cell cycle (Craig and Alt, 2004). Damage to chromosomes is manifested as breaks and fragments which appears as micronuclei in the rapidly proliferating cells (Hofer et al., 2000). Protecting living system from onslaughts of ionizing radiation is of paramount importance in radiation biology. Radioprotective agents are of significant importance in med- ical, industrial, environmental, military and space applications. Radioprotectors might reduce the cancer risk to population exposed to radiations directly or indirectly through industrial or military applications. The earlier studies were centered around in thiols, aminothiols and their derivatives and found the ‘gold standard’—the radioprotective drug amifostine or ethyol or WR 2127. Most of these protect cells, membranes and biomolecules such as DNA and proteins in vitro and showed promising results in laboratory studies but were of limited human application due to several factors such as toxicity at radio protecting doses and 1382-6689/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.etap.2008.02.004