• Toxicological Research
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• v.16 no.1
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• pp.9-16
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• 2000

Ginseng (the root of Panax ginseng C. A. Meyer, Araliaceae) has been used for traditional medicine in China, Korea, Japan and other Asian countries. It is most often used as a general tonic, and it involves a wide range of pharmacological actions, such as antiaging, adaptogen-like effect to foreign deleterious infringement, immunoenhancement, antistress, antitumor, and antioxidant actions. Red ginseng showed anticarcinogenic activity against various chemical carcinogens in mouse and cancer-preventive effect of human being as on mice in experimental and epidemiological studies. In the present study, we have found the protective properties of red ginseng against vinyl carbamate (VC) which is the proximate carcinogen of ethyl carbamate and its ultimate carcinogenic epoxides. Red ginseng exhibited dose-dependent inhibition on the mutagenci activities of boty VC in the presence of S9 mix and vinyl carbamate epoxide (VCO) without metabolic activation in Salmonella typhimurium TA1535. Formation of DNA adducts from VCO was also attenuated in the presence of red ginseng. Oral administration of red ginseng prior to the topical application of each of the above carcinogens and TPA treatment resulted in significant reduction in both incidence and multiplicity of skin tumors in mice. These results indicate that red ginseng possesses a strong chemopreventive effect against mouse skin carcinogenesis induced by VC or VCO.

• Environmental Mutagens and Carcinogens
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• v.17 no.2
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• pp.97-108
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• 1997

The drugs or xenobiotics introduced to the body, are detoxified through the process of biotransformation in the body. In this process, most of the insoluble compounds become more polar, soluble and easily excretable. But, parts of introduced materials are metabolized to highly reactive electrophilic carcinogens through activation pathways. These metabolites are toxic and can react with DNA, RNA and proteins which are nucleophilic compounds. The objective of this study is to illustrate the aleactivation pathways of two highly reactive epoxide compounds, vinyl carbamate epoxide (VCO) and 2'-(4-nitrophenoxy)oxirane (NPO). They are the ultimate electrophilic carcinogens of ethyl carbamate(urethane) and 4-nitrophenyl vinyl ether, respectively. In this research, we studied the inhibition of the mutagenic activities of VCO or NPO by nuchieophiles [glutahione(GSH) and N-acetylcysteine(NAC)], detoxifying enzymes[epoxide hydrolase and glutathione-S-transferase(GST)] and intracellular organelles (microsomes and cytosol). In addition we also tested the suppression of DNA adducts formation by GSH and NAC. The results are summerized as follow. 1. The microsomes and cytosol which contain epoxide hydrolase and GST, respectively, decreased the mutagenicity of VCO (74% and 95%, respecfivel), and NPO (35% and 93%, respectively). The nucleophilic GSH and NAC decreased the mutagenicity by 86% (VCO) and 80% (NPO), 76% (VCO) and 40% (NPO), respectively. 2. The purified epoxide hydrolase decreased the mutagenicity of two epoxides in a dose-dependent manner, and GSH also decreased the mutagenicity in the presence of GST. 3. Formation of two DNA adducts, 7-(2'-oxoethyi)guanine (OEG) and N2,3-ethenoguanine(EG), were compared in the presence of calf thymus DNA and epoxide (VCO or NPO) in vitro system. The amounts of DNA adducts were decreased in the presence of GSH (25% and 29% in VCO, 32% and 29% in NPO), and NAC (14% and 16% in VCO, 21% and 11% in NPO), respectively. From these results, it is concluded that the ultimate carcinogenic metabolites, VCO and NPO, can be made in the body, but much of them may be inactivated and detoxified by the nucleophilic GSH, NAC and detoxifying enzymes (epoxide hydrolase and GST). Therefore, by these mechanism, the formation of DNA adducts and mutagenic activities of these two epoxides may be lowered in vivo.