3-AMINO-1,4-DIMETHYL-5H-PYRIDO[4,3-B]INDOLE (TRP-P-1) INHIBITS THE REMOVAL OF BOTH CYCLOBUTANE DIMERS AND (6-4) PHOTOPRODUCTS FROM THE DNA OF ULTRAVIOLET-IRRADIATED ESCHERICHIA-COLI

Heterocyclic amines have been isolated from cooked foods and found to be mutagens and carcinogens. Among them, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) were also found to enhance UV-induced mutation frequencies in Escherichia coli at the concentrations where they were neither toxic nor mutagenic by themselves. Using an immunological method recently developed to detect UV-induced DNA damage, we investigated the inhibitory effect of Trp-P-1 on the removal of both cyclobutane dimers and (6-4)photoproducts from the DNA of UV-irradiated E.coli. Cells repaired 60% of the initial cyclobutane dimers within 30 min and 75% at 120 min after UV-irradiation. Furthermore, the same cells repaired 90% of the initial (6-4)photoproducts within 30 min. On the other hand, Trp-P-1 clearly showed inhibition of repair of both photolesions in a concentration-dependent manner. The levels of repair inhibition by Trp-P-1 were almost the same between cyclobutane dimers and (6-4)photoproducts. These results suggested that the enhancing effect of Trp-P-1 on UV-induced mutagenesis in E. coli stemmed from the inhibition of the removal of photolesions from the DNA.