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.

Green Tea Extract Modulates Actin Remodeling via Rho Activity in an In vitro Multistep Carcinogenic Model

“…The polyphenon E contains 80% to 98% total catechins by weight; the main component is EGCG, which comprises 50% to 75% of the material. Other catechins are present in levels ranging from f2% to 12% each, including epicatechin, epigallotechin, epicatechin-3-gallate, and gallotechin gallate (23). In this in vitro study, three concentration levels were examined in the cell lines (20,40, and 80 Ag/mL).…”

The cytogenetic effects of black tea and green tea on cultured human lymphocytes

“…Many studies have demonstrated that tea catechins could suppress the genotoxic activity of various carcinogens with both in vitro and in vivo systems (Kuroda, 1996;Sinha et al, 2005;Isbrucker et al, 2006). Chang et al, (2003) have shown that there is minimal genotoxic concern with a decaffeinated green tea catechin mixture. The antigenotoxic and anticlastogenic activities of the tea are mostly due to its antioxidant activity that inactivates the direct carcinogens.…”

Scientific Opinion on a Qualified Presumption of Safety (QPS) approach for the safety assessment of botanicals and botanical preparations

“…A green tea preparation (consisting of 85 to 95% total catechins (by weight) and more than 55% EGCG) was negative in the Ames test, the rat micronucleus assay, the UDS test, and the transgenic mouse mutation assay, but positive in the mouse lymphoma mutation assay (FDA, 2006;Chang et al, 2003). In an oral (gavage) carcinogenicity study, the same preparation was administered daily for 26 weeks to p53 transgenic mice at doses up to 500 mg/kg/day.…”