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 acid (vitamin C) on the direct clastogenicity of doxorubicin (Adriamycin) 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-treatment, 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) were found to exert an antimutagenic effect against the clastogenicity of doxorubicin (1.5 x 10(-2) nmol/ml) in all treatments at all concentrations. Ascorbic acid (10 nmol/ml) was effective in reducing the micronucleus levels only in the simultaneous treatment, when it was previously incubated with doxorubicin for 2 h at 37 degrees C before being introduced into the culture. Our results suggested a desmutagenic effect for alpha-hederin, chlorophyllin and ascorbic acid. Chlorophyllin acted also through a bio-antimutagenic mechanism and alpha-hederin seemed to induce metabolic enzymes, which inactivated doxorubicin. Preliminary studies showed that the effective antimutagenic concentrations of alpha-hederin, chlorophyllin and ascorbic acid had no clastogenic or aneugenic effects in human lymphocytes. No cytotoxicity was observed for the three antimutagenic agents either.
Amara-Mokrane
Y A
YA
Laboratoire de Biogénotoxicologie, Faculté de Médecine, France.
Lehucher-Michel
M P
MP
Balansard
G
G
Duménil
G
G
Botta
A
A
D000328:Adult; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002478:Cells, Cultured; D002735:Chlorophyllides / Q000494:pharmacology*; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes; D015162:Micronucleus Tests; D009828:Oleanolic Acid / Q000031:analogs & derivatives*; D012503:Saponins / Q000494:pharmacology*; D013997:Time Factors
D016587:Antimutagenic Agents; D002735:Chlorophyllides; D012503:Saponins; C010177:beta-hederin; D009828:Oleanolic Acid; D004317:Doxorubicin; C007020:chlorophyllin; D001205:Ascorbic Acid