Induction of DNA Recombination by Activated 3‐Amino‐1‐methyl‐5H‐pyrido43‐bindole

摘要

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 λ 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.