Shigeru Ozasa

Mutagenicity modulating effect of quercetin on aromatic amines and acetamides

The effect of quercetin on the mutagenicity of 32 kinds of aromatic amines and their acetamides were investigated using Salmonella typhimurium TA98 with a mammalian metabolic activation system (S9 mix). Quercetin enhanced the mutagenicity of the tricyclic aromatic amines (aminofluorene, aminoanthracene and aminophenanthrene) and their acetamides by 1.2-5.9-fold. Whereas, quercetin depressed the mutagenicity of aniline derivatives, biphenyl derivatives, and bi- and tetra-cyclic amino derivatives. The modulation of mutagenicity of Trp-P-1, Trp-P-2, Glu-P-1 and Glu-P-2 (heterocyclic amines) by quercetin were liable to be affected by the content of S9 in the S9 mix. It seems that quercetin does not have the same effect as norharman, because quercetin did not enhance the mutagenicity of aniline. It is suggested that the modulation of the mutagenicity of aromatic amines and acetamides is caused by the modulation of the balance between the mutagenic activation and inactivation in the metabolism of these amines and acetamides in the presence of quercetin. In this modulation, quercetin may participate through its effects on the promotion of N-hydroxylation and the inhibition of arylhydroxylation and transacylation. The presence of tricyclic aromatic rings of amines and acetamides is a structural requirement for the mutagenicity enhancement by quercetin.

Relationships between structure of nitrated arenes and their mutagenicity in Salmonella typhimurium; 2- and 2,7-nitro substituted fluorene, phenanthrene and pyrene.

In order to elucidate the mechanisms of mutagenic activation of nitroarenes, we studied the relationships between the mutagenic potency and chemical structure of 2-nitro- and 2,7-dinitro-arenes including nitrated fluorene (Fl), dihydrophenanthrene (DHPh), phenanthrene (Ph), tetrahydropyrene (THPy), dihydropyrene (DHPy) and pyrene (Py) together with 9-NO2-Ph, 1-NO2-Py and 1.3-diNO2-Py. The mutagenicity tests were carried out on Salmonella typhimurium TA98, TA98NR and TA98/1,8-DNP6 in the absence of S9 mix. The order of mutability of mononitro- and dinitro-arenes in TA98 is as given below: 2-NO2-THPy less than 2-NO2-Fl less than 2-NO2-DHPh less than 9-NO2-Ph less than 2-NO2-Ph less than 2-NO2-DHPy less than 1-NO2-Py less than 2-NO2-Py, and 2,7-diNO2-DHPh less than 2,7-diNO2-Fl less than 2,7-diNO2-THPy less than 2,7-diNO2-Ph less than 2,7-diNO2-DHPy less than 2,7-diNO2-Py less than 1,3-diNO2-Py. 9-NO2-Ph and 1-NO2-Py, which have been detected in environmental samples, are not as potent mutagens as 2-nitrated phenanthrene and pyrene, respectively. 2-NO2THPy (37.7 rev/nmole) was a weak mutagen, but 2,7-diNO2-THPy (3197 rev/nmole) was as potent a mutagen as 2,7-diNO2 (3925 rev/nmole). Tetrahydropyrene has a twisted form in its structure. 1,3-diNO2-Py (99660 rev/nmole) was more mutagenic than 2,7-diNO2-Py (37960.0 rev/nmole), and their mutagenicities were correlated with the behavior of the K-band in their UV spectra by the introduction of nitro groups on pyrene.