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.

3‐amino‐1‐methyl‐5H‐pyrido[4,3‐b]indole

2‐hydroxyaminofluorene

4‐hydroxyaminoquinoline n class="Chemical">N‐oxide

3‐hydroxyamino‐1‐methyl‐5H‐pyrido[4,3‐b]indole

3‐n class="Chemical">nitroso‐1‐methyl‐5H‐pyrido[4,3‐b]indole

3‐nitro‐1‐methyl‐5H‐pyrido[4,3‐b]indole

N‐methyl‐N1 ‐nitro‐N‐nitrosoguanidine

4‐nitroquino‐line n class="Chemical">N‐oxide

phthalic acid mono‐n‐butyl ester cupric salt

sister chromatid exchange

superoxide dis‐mutase

ultraviolet