Inhibitory effect of chlorophyll on the genotoxicity of 3-amino-1-methyl-5H-pyrido[4,3-b indole (Trp-P-2)

Abstract

Genotoxicity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) on Drosophila was suppressed by chlorophyll. Using the wing hair spot test, we found that the formation of mutant hairs in adult flies as a result of feeding them with Trp-P-2 in their larval stage was efficiently inhibited by coadministration of chlorophyll. The decrease in the spot frequencies was dependent on the dose of chlorophyll, and at the highest dose used, where the ratio in weight of Trp-P-2 to chlorophyll was 1:80, a complete prevention of the small single-spot formation was observed. A similar inhibitory effect was detected for chlorophyllin, the chromophore of chlorophyll. In the studies to investigate the mechanism of inhibition, we observed that the mutagenicity of 3-hydroxy-amino-1-methyl-5H-pyrido[4,3-b]indole [Trp-P-2(NHOH)], the metabolically activated form of Trp-P-2, in Salmonella typhimurium TA98 was suppressed effectively with chlorophyll and chlorophyllin. We also found that chlorophyll and chlorophyllin can produce complexes with Trp-P-2 and Trp-P-2(NHOH). A straightforward mechanism of these inhibitions is that Trp-P-2 [and Trp-P-2(NHOH)] becomes no longer available to organisms on forming the chlorophyll complex.

Hetero-association of aromatic molecules in aqueous solution

“…The first detailed investigation of CHL-drug and related systems was performed with respect to various mutagen molecules [39,44,[198][199][200][201][202][203][204], and more recent studies [41,156,157,205,206] have extended the set of drugs to antitumor antibiotics and some other types of mutagens. It was found that chlorophylls are able to form face-toface complexes with planar molecules, and the addition of methyl groups above or below the plane of the mutagen molecule interferes sterically with overlapping CHL/ mutagen ring systems, thus reflecting the importance of 'structural complementarity' in hetero-association [156].…”

Heterocyclic Aromatic Amines Heterocomplexation with Biologically Active Aromatic Compounds and Its Possible Role in Chemoprevention

“…On the other hand, CHL was demonstrated to protect against mutagenic activity of direct-acting N-hydroxy HCAs derivatives: Trp-P-2[NHOH] [44], N-OH-IQ [45], and other direct-acting aromatic compounds: benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) [46] and aflatoxin B 1 -8,9-epoxide [47]. In contrary, no inhibitory effect of CHL was observed against small, nonplanar alkylating agents, N -methyl-Nnitrosourea (MNU) and ethyl methanesulfonate (EMS) [46].…”

Chemopreventive properties of chlorophylls towards aflatoxin B1: a review of the antimutagenicity and anticarcinogenicity data in rainbow trout

“…However, in contrast to CHL, which is highly water soluble, lipophilic natural chlorophylls complex less effectively with carcinogens under the aqueous conditions of many in vitro assays. A mixture of chlorophylls a and b was shown to exhibit antimutagenic activity in the Salmonella assay by a mechanism involving complex formation [19], and purified chlorophyll a protected against the formation of DNA adducts in isolated hepatocytes by interfering with carcinogen activation [20].…”