PROTECTIVE EFFECTS OF ALPHA-HEDERIN, CHLOROPHYLLIN AND ASCORBIC-ACID TOWARDS THE INDUCTION OF MICRONUCLEI BY DOXORUBICIN IN CULTURED HUMAN-LYMPHOCYTES

The influence of alpha-hederin (a saponin isolated from Hedera helix), chlorophyllin, the sodium-copper salt of chlorophyll, and ascorbic ac id (vitamin C) on the direct clastogenicity of doxorubicin (Adriamycin (R)) was investigated in vitro in human lymphocytes for the induction of micronuclei, In order to determine a possible mechanism of action responsible for the antimutagenic activity, treatments were performed for the three substances at different times of the culture (pre-treatm ent, simultaneous and post-treatment). Alpha-hederin (1.3 x 10(-2), 0. 13, 1.3 and 13 nmol/ml) and chlorophyllin (0.14, 1.4 and 14 nmol/ml) w ere found to exert an antimutagenic effect against the clastogenicity of doxorubicin (1.5 x 10(-2) nmol/ml) in all treatments at all concent rations, Ascorbic acid (10 nmol/ml) was effective in reducing the micr onucleus levels only in the simultaneous treatment, when it was previo usly incubated with doxorubicin for 2 h at 37 degrees C before being i ntroduced into the culture, Our results suggested a desmutagenic effec t for alpha-hederin, chlorophyllin and ascorbic acid, Chlorophyllin ac ted also through a bio-antimutagenic mechanism and alpha-hederin seeme d to induce metabolic enzymes, which inactivated doxorubicin, Prelimin ary studies showed that the effective antimutagenic concentrations of alpha-hederin, chlorophyllin and ascorbic acid had no clastogenic or a neugenic effects in human lymphocytes, No cytotoxicity was observed fo r the three antimutagenic agents either.