The suppressive effect of (-)-epigallocatechin gallate (EGCG), the major polyphenolic constituent present in green tea, on 7,12-dimethylbenz [a]anthracene (DMBA)-induced chromosome aberrations (CA) in rat bone marrow cells was studied. Rats given EGCG before the DMBA injection displayed a considerably suppressed frequency of DMBA-induced CA in their bone marrow cells. The suppressive effect of EGCG (60 mg/kg body weight) given 24 h before was observed 24, 30, 48 and 72 h after the DMBA injection, but not at the early period (6, 12 and 18 h) after the DMBA treatment. On the other hand, EGCG (60 mg/kg body weight) given 0.5 h before DMBA suppressed DMBA-induced CA at all periods after the DMBA injection. The suppression of EGCG given 24 h or 0.5 h before was observed for all doses of DMBA (25, 50, 75 and 100 mg/kg) investigated. EGCG given at 60 mg/kg body weight 0.5 h before the DMBA injection showed greater suppressive effect than the same dose given 24 h before. The suppressive effect of EGCG given 0.5 h before was dosedependent in the range of 20 60 mg/kg body weight. Methyl methanesulfonate (MMS: direct-acting carcinogen)-induced CA were not suppressed by EGCG.The administration of dehydroepiandrosterone (DHEA), a typical substrate for hydroxysteroid sulfotransferases, 0.5 h before DMBA injection also significantly suppressed DMBA-induced CA but DHEA given 24 h before did not.These results suggest that EGCG has two different suppression mechanisms for DMBA-induced CA depending on the administration time. The suppression of DMBA-induced CA by EGCG given 24 h or 0.5 h before may result from the modification of microsomal enzyme system or the inhibition of sulfotransferase activity by EGCG, respectively. We have previously reported (Ito et al., 1989) that the administration of GTE or GTP mixture before aflatoxin B 1 (AFB 1 ) injection in rats significantly suppressed AFB 1 -induced chromosome aberrations (CA) in bone marrow cells. Furthermore, we have reported (Ito and Ito, 2001) the suppressive effect of EGCG on AFB 1 -induced CA in rat bone marrow cells. EGCG given 24 h before the AFB 1 injection suppressed AFB 1 -induced CA but not when given 2 h before; the same was true for GTE or GTP mixture. This suppression seems to be due to modification of the microsomal enzyme system by EGCG.In this study, we investigated the suppressive effect of EGCG on CA induced by 7,12-dimethylbenz[a]anthracene (DMBA: indirect-acting carcinogen, as is AFB 1 ) and by methyl methanesulfonate (MMS: direct-acting carcinogen, needs no metabolic activation).
Materials and Methods
ChemicalsEGCG was purchased from Kurita Kogyo Co. (Tokyo, Japan). DMBA, dehydroepiandrosterone (DHEA) and colchicine were obtained from Wako Pure Chemicals Co. (Tokyo, Japan), MMS was from Aldrich (Milwaukee, WI), and dimethyl fulfoxide (DMSO: spectrophotometric grade) was from E. Merck A.G., (Darmstadt, F.R.G.).
Animal experimentsMale rats of the Wistar strain (Charles River Japan, Inc., Kanagawa, Japan), aged 28 35 days and weighing 80 110 g, were used. Each...