Inhibitory effect of chlorophyll on the genotoxicity of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2).
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.
Negishi
T
T
Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Arimoto
S
S
Nishizaki
C
C
Hayatsu
H
H
D000818:Animals; D002243:Carbolines / Q000037:antagonists & inhibitors*; D055598:Chemical Phenomena; D002621:Chemistry; D002734:Chlorophyll / Q000494:pharmacology*; D002735:Chlorophyllides / Q000494:pharmacology; D004249:DNA Damage; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009154:Mutation / Q000187:drug effects*; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013057:Spectrum Analysis; D014921:Wings, Animal
D002243:Carbolines; D002735:Chlorophyllides; D002734:Chlorophyll; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; C007020:chlorophyllin