Chlorophyllin protects cells from the cytostatic and cytotoxic effects of quinacrine mustard but not of nitrogen mustard

Chlorophyllin (CHL), the sodium and copper salt of chlorophyll, is capable of inhibiting the mutagenic activity of many chemical compounds. Several me chanisms have been advanced to explain the antimutagenic activity of CHL, i ncluding its antioxidant properties and its ability to form complexes with mutagens. The present study was designed to reveal whether the heterocyclic aromatic nature of a potential mutagen is essential to its sensitivity to CHL. Toward this end, the inhibitory effect of CHL on two compounds of simi lar chemical reactivity (mustards), that either embodied an aromatic struct ure (quinacrine mustard; QM) or did not (nitrogen mustard; NM), were compar ed. Human leukemic HL-60 and breast carcinoma MCF-7 cells were treated with QM or NM in the absence or presence of various concentrations of CI-IL. Bo th QM and NM when administered for 1-2 h at micromolar concentrations exert ed similar effects; both arrested cells in G(2) phase of the cell cycle, in duced apoptosis and reduced the clonogenicity of MCF-7 cells. The simultane ous addition of 0.22 M CHL to cultures receiving QM virtually abolished the QM-induced inhibition of cell growth acid clonogenicity. In contrast, CHL had no effect on reducing the cytostatic or cytotoxic activity of NM. CHL a lone, at a concentration of 0.22 M, had minimal effect on growth of HL-60 c ells slightly perturbing their progression through G(2). The results are co nsistent with the model that explains the inhibition of the activity of mut agens or antitumor drugs with aromatic structures by CHL as mediated by its ability to sequester these molecules within heterologous mutagen:CHL compl exes that are maintained by stacking interactions. Therefore, excess of chl orophyll in the diet, by sequestering aromatic mutagens (or antitumor drugs with a heterocyclic structure, if taken orally), may inhibit their accessi bility to cells, thereby reducing their activity.