Enhancing effect of heterocyclic amines and beta-carbolines on UV or chemically induced mutagenesis in E. coli.

Most heterocyclic amines and beta-carbolines--harman, norharman, harmine, harmaline--enhanced UVC (254 nm) induced mutagenesis without microsomal activation in E. coli B/r WP2. 3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) was most effective and increased UVAB (295-400 nm) induced mutations as well as UVC induced ones. Trp-P-1 enhanced the frequencies of mutations induced by not only UV but also 4-nitroquinoline-1-oxide (4NQO) or 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide (AF2), while it showed little effect on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or gamma-ray induced mutagenesis. Trp-P-1 decreased the survival of UVC irradiated cells of CM571recA. However, these effects of Trp-P-1 on UVC induced mutagenesis and lethality were not observed in WP2suvrA which is excision repair deficient. The alkaline sucrose gradient sedimentation analysis demonstrated that Trp-P-1 blocked the incision step in DNA excision repair. Further, pretreatment with Trp-P-1 before UVC irradiation showed no effect on UVC induced mutagenesis. Similar effects were also seen in the case of harman or norharman. These results suggest that heterocyclic amines and beta-carbolines inhibit DNA excision repair directly or indirectly, thus enhancing UV or chemically induced mutagenesis.