title: Genotoxicity and toxicity of the potential cancer-preventive agent polyphenon E.
abstract: The potential health benefits of green tea continue to attract public and scientific interests and are attributed in part to polyphenolic catechin constituents. Polyphenon E (Poly E) is a decaffeinated green tea catechin mixture containing about 50% epigallocatechin gallate and 30% other catechins. We evaluated the toxicity and genotoxicity of Poly E by using two in vitro assays: bacterial mutagenesis in a Salmonella typhimurium-E. coli assay and the L5178Y mouse lymphoma cell thymidine kinase (Tk) gene mutation assay. In addition, we used two in vivo genotoxicity assays: the mouse micronucleus assay and the Big Blue cII transgenic mouse mutation assay. Repeat-dose toxicity evaluations were performed in mice in parallel with the Big Blue transgenic mutation assays. No significant increases in the revertant colonies were found in the bacterial mutagenesis assay, but a significant increase in the mutant frequency (MF) at the Tk locus was observed in the mouse lymphoma test system. We observed toxicity in mice when Poly E was administered at doses of 2,000 mg/kg/day. Lower doses produced no significant increases in micronucleated erythrocytes in the bone marrow of Swiss-Webster mice and no significant increases in cII transgene MF in the liver, lung, or spleen compared with controls. These results indicate that Poly E, although toxic at high doses (2,000 mg/kg/day), poses minimal genotoxic concern. In addition, these studies highlight the importance of using both in vitro and in vivo systems in genetic toxicity screening of pharmaceuticals before they are administered to humans.
authors.affiliation: Biopharmaceutical Development Division, SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA. pchang@sri.com
authors.forename: Polly Y
authors.initials: PY
authors.lastname: Chang
authors.forename: Jon
authors.initials: J
authors.lastname: Mirsalis
authors.forename: Edward S
authors.initials: ES
authors.lastname: Riccio
authors.forename: James P
authors.initials: JP
authors.lastname: Bakke
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Lee
authors.forename: Julie
authors.initials: J
authors.lastname: Shimon
authors.forename: Sandra
authors.initials: S
authors.lastname: Phillips
authors.forename: David
authors.initials: D
authors.lastname: Fairchild
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Hara
authors.forename: James A
authors.initials: JA
authors.lastname: Crowell
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects / Q000235:genetics; D001854:Bone Marrow Cells / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives / Q000633:toxicity*; D004435:Eating; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D005260:Female; D008223:Lymphoma / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015162:Micronucleus Tests / Q000379:methods; D009152:Mutagenicity Tests / Q000379:methods; D009929:Organ Size / Q000187:drug effects; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013937:Thymidine Kinase / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D016588:Anticarcinogenic Agents; D002392:Catechin; D013937:Thymidine Kinase; C472086:polyphenon E