Amara-Mokrane Y A, Lehucher-Michel M P, Balansard G, Duménil G, Botta A
Laboratoire de Biogénotoxicologie, Faculté de Médecine, France.
Mutagenesis. 1996 Mar;11(2):161-7. doi: 10.1093/mutage/11.2.161.
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.
研究了α-常春藤皂苷（从常春藤中分离出的一种皂苷）、叶绿酸（叶绿素的铜钠盐）和抗坏血酸（维生素C）对阿霉素（多柔比星）直接致染色体断裂作用的影响，该实验在体外人淋巴细胞中进行，以诱导微核形成。为了确定负责抗诱变活性的可能作用机制，对这三种物质在培养的不同时间（预处理、同时处理和后处理）进行了处理。结果发现，在所有浓度的所有处理中，α-常春藤皂苷（1.3×10⁻²、0.13、1.3和13 nmol/ml）和叶绿酸（0.14、1.4和14 nmol/ml）对阿霉素（1.5×10⁻² nmol/ml）的致染色体断裂作用均具有抗诱变作用。抗坏血酸（10 nmol/ml）仅在同时处理时有效降低微核水平，即它在37℃下与阿霉素预孵育2小时后再引入培养物中。我们的结果表明α-常春藤皂苷、叶绿酸和抗坏血酸具有去诱变作用。叶绿酸还通过生物抗诱变机制发挥作用，α-常春藤皂苷似乎诱导了使阿霉素失活的代谢酶。初步研究表明，α-常春藤皂苷、叶绿酸和抗坏血酸的有效抗诱变浓度在人淋巴细胞中没有致染色体断裂或致非整倍体作用。这三种抗诱变剂也未观察到细胞毒性。
