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 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.
Mori
T
T
RI Center, Nara Medical University, Kashihara, Japan.
Shimoi
K
K
Sasaki
Y F
YF
Wakabayashi
K
K
Nagao
M
M
Kinae
N
N
D002243:Carbolines / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects*; D004269:DNA, Bacterial / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D004926:Escherichia coli; D009153:Mutagens / Q000633:toxicity*; D010777:Photochemistry; D011740:Pyrimidine Dimers; D014466:Ultraviolet Rays
D002243:Carbolines; D004269:DNA, Bacterial; D009153:Mutagens; D011740:Pyrimidine Dimers; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole