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 E. coli

Heterocyclic amines have been isolated from cooked foods andfound 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 frequenciesin Escherichia coli at the concentrations where they were neithertoxic nor mutagenic by themselves. Using an immunological methodrecently developed to detect UV-induced DNA damage, we investigatedthe inhibitory effect of Trp-P-1 on the removal of both cyclobutanedimers and (6–4)photo-products from the DNA of UV-irradiatedE.coli. Cells repaired 60% of the initial cyclobutane dimerswithin 30 min and 75% at 120 min after UV-irradiation. Furthermore,the same cells repaired 90% of the initial (6–4)photoproductswithin 30 min. On the other hand, Trp-P-1 clearly showed inhibitionof repair of both photolesions in a concentration-dependentmanner. The levels of repair inhibition by Trp-P-1 were almostthe same between cyclobutane dimers and (6–4)photoproducts.These results suggested that the enhancing effect of Trp-P-1on UV-induced mutagenesis in E.coli stemmed from the inhibitionof the removal of photolesions from the DNA.