Inhibition of DNA adduct formation and mutagenic action of 3-amino-1-methyl-5h-pyrido[4,3-b]indole by chlorophyllin-chitosan in rpsL transgenic mice.
We have studied the inhibitory effect of chlorophyllin-chitosan (Chl-Chi) complex, an insoluble form of chlorophyllin, on the DNA adduct formation and mutagenesis by a heterocyclic food mutagen-carcinogen, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), in mice carrying the E. coli rpsL gene as a mutagenesis reporter. Upon administration of a diet containing 0.002% or 0.01% Trp-P-2, DNA adducts were formed in various tissues in a dose-dependent manner, with the maximum level observed in the liver. Addition of 3% Chl-Chi to the diet reduced the Trp-P-2 adduct by up to 90%. The rpsL mutant frequencies increased significantly in both the liver and spleen upon administration of a 0.01% Trp-P-2 diet. Addition of Chl-Chi to the diet decreased these induced mutant frequencies to the background level. No harmful effect of Chl-Chi was detected during these experiments. The results show that Chl-Chi may be a candidate chemopreventive agent against the genotoxic action of Trp-P-2, and possibly also other aromatic carcinogens in the diet.
Anzai
N
N
Gene Research Center, Okayama University, 1-1-1 Tsushima-Naka, Okayama 700-8530, Japan. knegishi@cc.okayama-u.ac.jp
Taniyama
T
T
Nakandakari
N
N
Sugiyama
C
C
Negishi
T
T
Hayatsu
H
H
Negishi
K
K
D000818:Animals; D002243:Carbolines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D002686:Chitin / Q000031:analogs & derivatives / Q000494:pharmacology*; D048271:Chitosan; D002735:Chlorophyllides / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D018736:DNA Adducts / Q000187:drug effects*; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D029968:Escherichia coli Proteins; D005787:Gene Frequency; D008113:Liver Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008822:Mice, Transgenic; D016296:Mutagenesis / Q000187:drug effects*; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D000091243:Ribosomal Protein S9; D012269:Ribosomal Proteins / Q000235:genetics*
D002243:Carbolines; D002735:Chlorophyllides; D018736:DNA Adducts; D004338:Drug Combinations; D029968:Escherichia coli Proteins; D009153:Mutagens; D000091243:Ribosomal Protein S9; D012269:Ribosomal Proteins; C000717190:RpsI protein, E coli; C034212:ribosomal protein S12; D002686:Chitin; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D048271:Chitosan; C007020:chlorophyllin