Induction of DNA recombination by activated 3-amino-1-methyl-5H-pyrido[4,3-b]indole.
To investigate the genotoxic properties of a food-derived carcinogen, 3-amino-1-methyl-5H-pyrido-[4,3-b]indole (Trp-P-2), we have tested whether Trp-P-2 and its metabolically transformed products can induce DNA recombinations. Trp-P-2 is a strong mutagen and its activated form, the N-hydroxylated derivative, Trp-P-2(NHOH), is known to form DNA adducts and cause DNA chain cleavage. Using a system in which phage lambda undergoes recombination inside host Escherichia coli, we have found that Trp-P-2(NHOH), but not Trp-P-2 itself, can induce recombination. A nitroso derivative of Trp-P-2, Trp-P-2(NO), which can be reduced intracellularly to form Trp-P-2(NHOH), also induced recombination. Active oxygens are implicated in this recombinogenic action, since Trp-P-2(NHOH) is known to undergo spontaneous oxidative degradation, generating active oxygen radicals which can cause DNA chain cleavages. 4-Hydroxyaminoquinoline N-oxide and phenyl-hydroxylamine also showed recombinogenic actions in this assay system; hence, it is suspected that aromatic amine-type carcinogens have this property in common.
Hiramoto
K
K
Graduate School of Natural Science and Technology, Okayama University.
Kanamitsu
S
S
Negishi
K
K
Ikeda
H
H
Hayatsu
H
H
D010582:Bacteriophage lambda / Q000187:drug effects* / Q000528:radiation effects; D002243:Carbolines / Q000494:pharmacology*; D002273:Carcinogens / Q000494:pharmacology*; D004249:DNA Damage; D004279:DNA, Viral / Q000187:drug effects* / Q000528:radiation effects; D004926:Escherichia coli / Q000821:virology; D009153:Mutagens / Q000494:pharmacology*; D011995:Recombination, Genetic
D002243:Carbolines; D002273:Carcinogens; D004279:DNA, Viral; D009153:Mutagens; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole