In vivo genotoxicity of a novel heterocyclic amine, aminobenzoazepinoquinolinone-derivative (ABAQ), produced by the Maillard reaction between glucose and l-tryptophan.

We recently demonstrated that a novel heterocyclic amine, 5-amino-6-hydroxy-8H-benzo[6,7]azepino[5,4,3-de]quinolin-7-one (ABAQ), is produced from glucose and l-tryptophan by the Maillard reaction at physiological temperature and pH, and that ABAQ was strongly mutagenic for Salmonella strains in the presence of S9 mix. Here, we present the results of three in vivo genotoxicity assays of ABAQ. The comet assay revealed that DNA damage was significantly increased in the livers, kidneys, lungs, and bone marrows of ICR mice, 3h after i.p. injection of ABAQ (50mg/kg body weight (bw)). To evaluate clastogenicity, the peripheral blood micronucleus test was performed, also in ICR mice. ABAQ induced micronucleated reticulocytes (MNRETs) in a dose-dependent manner; the frequency of MNRETs was significantly elevated at all i.p. doses (12.5, 25, and 50mg/kg bw) after 48h. To investigate the mutagenicity of ABAQ in vivo, gpt delta transgenic mice were treated with five consecutive administrations of ABAQ by gavage at doses of 25 or 50mg/kg per week for 3 weeks. The frequencies of gpt mutations (MF) in the liver of mice increased significantly compared with controls, in a dose-dependent manner. No significant increase of gpt MF was detected in the kidneys. Base substitutions predominated; both G:C→A:T and A:T→C:G mutations were significantly increased by ABAQ. The Spi(-) MF was also significantly increased in the liver after ABAQ treatment. If formed in vivo, ABAQ may give rise to adverse genotoxic effects.

Triple tandem catalyst mixtures for the synthesis of polyethylenes with varying structures.

Tandem catalysis in a single medium presents challenges and opportunities for creating novel synthetic protocols. Thus far, only two homogeneous catalysts have been used in tandem. Herein, we report that it is possible to coordinate the action of three well-defined homogeneous catalysts to produce a wide range of branched polyethylenes from a single monomer. Thus, ([(eta(5)-C(5)Me(4))SiMe(2)(eta(1)-NCMe(3))]TiMe)(MeB(C(6)F(5))(3)) (1), [(C(6)H(5))(2)PC(6)H(4)C(OB(C(6)F(5))(3))O-kappa(2)P,O]Ni(eta(3)-CH(2)C(6)H(5)) (2), and ((H(3)C)C[N(C(6)H(5))]C[O-B(C(6)F(5))(3)][N(C(6)H(5))]-kappa(2)N,N)Ni(eta(3)-CH(2)C(6)H(5)) (3) react with ethylene to produce branched polyethylene with structures that cannot be obtained using a single- or a two-component catalyst combination. The properties of the polyethylene depend on the ratio of the three catalysts. High-throughput screening techniques proved essential for optimizing reaction conditions and for probing how the catalyst composition influences the polymer properties.