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Antimutagenic potency of chlorophyllin in the salmonella assay and its correlation with binding constants of mutagen‐inhibitor complexes
Author(s) -
Dashwood Roderick,
Guo Dexin
Publication year - 1993
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.2850220309
Subject(s) - chlorophyllin , mutagen , carcinogen , potency , chemistry , ames test , antimutagen , quinoline , stereochemistry , genotoxicity , biochemistry , salmonella , in vitro , biology , toxicity , chlorophyll , organic chemistry , genetics , bacteria
Chlorophyllin (CHL) is a water‐soluble salt of chlorophyll that exhibits antimutagenic activity in short‐term genotoxicity assays and inhibits carcinogen‐DNA binding in vivo. The antimutagenic potency of CHL was studied against several structurally related heterocyclic amines using the Salmonella assay. The mutagens included 2‐amino‐3‐methylimidazo[4,5,‐ f ]‐quinoline (IQ) and seven related IQ‐type compounds, and 3‐amino‐1‐methyl‐5 H ‐pyrido[4,3‐ b ]indole (Trp‐P‐2) and three additional non‐IQ‐type compounds. No relationship was observed between mutagenic potency (revertants/ng mutagen) and antimutagenic potency when expressed in terms of the CHL dose/plateinhibiting mutagenicity by 50 percent (l 50 ). However, a correlation was observed between mutagenic potency and the mole ratio of CHL to mutagen giving 50% inhibition (MR 50 ), with most mutagens requiring several hundredfold to several thousandfold molar excess of CHL for inhibition. In spectrophotometric studies, CHL formed noncovalent molecular complexes with the heterocyclic amines, with binding constants in the range 3–13 x 10 3 M −1 . Binding constants were inversely correlated with l 50 and MR 50 values, i.e., with increasing strength of complex formation less CHL/plate and a lower mole ratio of CHL to mutagen was required to inhibit mutagenicity. The results support an inhibitory mechanism in which chlorophylls operate as “interceptor molecules,” interacting with carcinogens and mutagens directly and limiting their bioavailability. © 1993 Wiley‐Liss, Inc.